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  • American Association for the Advancement of Science (AAAS)  (316)
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  • 1
    Publication Date: 2016-01-23
    Description: Mono-ubiquitination of Fancd2 is essential for repairing DNA interstrand cross-links (ICLs), but the underlying mechanisms are unclear. The Fan1 nuclease, also required for ICL repair, is recruited to ICLs by ubiquitinated (Ub) Fancd2. This could in principle explain how Ub-Fancd2 promotes ICL repair, but we show that recruitment of Fan1 by Ub-Fancd2 is dispensable for ICL repair. Instead, Fan1 recruitment--and activity--restrains DNA replication fork progression and prevents chromosome abnormalities from occurring when DNA replication forks stall, even in the absence of ICLs. Accordingly, Fan1 nuclease-defective knockin mice are cancer-prone. Moreover, we show that a Fan1 variant in high-risk pancreatic cancers abolishes recruitment by Ub-Fancd2 and causes genetic instability without affecting ICL repair. Therefore, Fan1 recruitment enables processing of stalled forks that is essential for genome stability and health.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770513/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770513/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lachaud, Christophe -- Moreno, Alberto -- Marchesi, Francesco -- Toth, Rachel -- Blow, J Julian -- Rouse, John -- WT096598MA/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):846-9. doi: 10.1126/science.aad5634. Epub 2016 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK. ; Centre for Gene Regulation and Expression, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK. ; School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK. ; Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK. j.rouse@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797144" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Chromosome Aberrations ; DNA Repair ; *DNA Replication ; Endodeoxyribonucleases/genetics/*metabolism ; Fanconi Anemia Complementation Group D2 Protein/genetics/*metabolism ; Female ; Gene Knock-In Techniques ; Genetic Predisposition to Disease ; Genomic Instability/*genetics ; Liver Neoplasms/genetics/pathology ; Lung Neoplasms/genetics/pathology ; Lymphoma/genetics/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Pancreatic Neoplasms/*genetics ; *Ubiquitination
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  • 2
    Publication Date: 2016-04-02
    Description: The recent rapid spread of Zika virus and its unexpected linkage to birth defects and an autoimmune neurological syndrome have generated worldwide concern. Zika virus is a flavivirus like the dengue, yellow fever, and West Nile viruses. We present the 3.8 angstrom resolution structure of mature Zika virus, determined by cryo-electron microscopy (cryo-EM). The structure of Zika virus is similar to other known flavivirus structures, except for the ~10 amino acids that surround the Asn(154) glycosylation site in each of the 180 envelope glycoproteins that make up the icosahedral shell. The carbohydrate moiety associated with this residue, which is recognizable in the cryo-EM electron density, may function as an attachment site of the virus to host cells. This region varies not only among Zika virus strains but also in other flaviviruses, which suggests that differences in this region may influence virus transmission and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845755/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845755/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sirohi, Devika -- Chen, Zhenguo -- Sun, Lei -- Klose, Thomas -- Pierson, Theodore C -- Rossmann, Michael G -- Kuhn, Richard J -- R01 AI073755/AI/NIAID NIH HHS/ -- R01 AI076331/AI/NIAID NIH HHS/ -- R01AI073755/AI/NIAID NIH HHS/ -- R01AI076331/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):467-70. doi: 10.1126/science.aaf5316. Epub 2016 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA. ; Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27033547" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cryoelectron Microscopy ; Glycosylation ; Humans ; Molecular Sequence Data ; Protein Structure, Tertiary ; Viral Envelope Proteins/chemistry/ultrastructure ; Viral Matrix Proteins/chemistry/ultrastructure ; Zika Virus/*chemistry/*ultrastructure
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  • 3
    Publication Date: 2016-04-16
    Description: The nuclear pore complex (NPC) controls the transport of macromolecules between the nucleus and cytoplasm, but its molecular architecture has thus far remained poorly defined. We biochemically reconstituted NPC core protomers and elucidated the underlying protein-protein interaction network. Flexible linker sequences, rather than interactions between the structured core scaffold nucleoporins, mediate the assembly of the inner ring complex and its attachment to the NPC coat. X-ray crystallographic analysis of these scaffold nucleoporins revealed the molecular details of their interactions with the flexible linker sequences and enabled construction of full-length atomic structures. By docking these structures into the cryoelectron tomographic reconstruction of the intact human NPC and validating their placement with our nucleoporin interactome, we built a composite structure of the NPC symmetric core that contains ~320,000 residues and accounts for ~56 megadaltons of the NPC's structured mass. Our approach provides a paradigm for the structure determination of similarly complex macromolecular assemblies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Daniel H -- Stuwe, Tobias -- Schilbach, Sandra -- Rundlet, Emily J -- Perriches, Thibaud -- Mobbs, George -- Fan, Yanbin -- Thierbach, Karsten -- Huber, Ferdinand M -- Collins, Leslie N -- Davenport, Andrew M -- Jeon, Young E -- Hoelz, Andre -- 5 T32 GM07616/GM/NIGMS NIH HHS/ -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- R01 GM111461/GM/NIGMS NIH HHS/ -- R01-GM111461/GM/NIGMS NIH HHS/ -- T32 GM007616/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):aaf1015. doi: 10.1126/science.aaf1015. Epub 2016 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. ; Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. hoelz@caltech.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081075" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Cytoplasm/metabolism ; Electron Microscope Tomography ; Fungal Proteins/chemistry/genetics/metabolism ; Humans ; Molecular Sequence Data ; Nuclear Pore/chemistry/*metabolism/*ultrastructure ; Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism ; *Protein Interaction Maps ; Protein Structure, Tertiary ; Protein Subunits/chemistry/genetics/metabolism
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  • 4
    Publication Date: 2016-02-27
    Description: Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corti, Davide -- Misasi, John -- Mulangu, Sabue -- Stanley, Daphne A -- Kanekiyo, Masaru -- Wollen, Suzanne -- Ploquin, Aurelie -- Doria-Rose, Nicole A -- Staupe, Ryan P -- Bailey, Michael -- Shi, Wei -- Choe, Misook -- Marcus, Hadar -- Thompson, Emily A -- Cagigi, Alberto -- Silacci, Chiara -- Fernandez-Rodriguez, Blanca -- Perez, Laurent -- Sallusto, Federica -- Vanzetta, Fabrizia -- Agatic, Gloria -- Cameroni, Elisabetta -- Kisalu, Neville -- Gordon, Ingelise -- Ledgerwood, Julie E -- Mascola, John R -- Graham, Barney S -- Muyembe-Tamfun, Jean-Jacques -- Trefry, John C -- Lanzavecchia, Antonio -- Sullivan, Nancy J -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. ; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. ; Humabs BioMed SA, 6500 Bellinzona, Switzerland. ; National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. njsull@mail.nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917593" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Antibodies, Monoclonal/*administration & dosage/immunology/isolation & ; purification ; Antibodies, Neutralizing/*administration & dosage/immunology/isolation & ; purification ; Antibodies, Viral/*administration & dosage/immunology/isolation & purification ; Clinical Trials as Topic ; Disease Outbreaks ; Ebolavirus/*immunology ; Female ; Hemorrhagic Fever, Ebola/epidemiology/*prevention & control ; Humans ; Macaca ; Male ; Molecular Sequence Data ; Survivors
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  • 5
    Publication Date: 2016-02-26
    Description: T cell-mediated destruction of insulin-producing beta cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in beta cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in beta cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in beta cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delong, Thomas -- Wiles, Timothy A -- Baker, Rocky L -- Bradley, Brenda -- Barbour, Gene -- Reisdorph, Richard -- Armstrong, Michael -- Powell, Roger L -- Reisdorph, Nichole -- Kumar, Nitesh -- Elso, Colleen M -- DeNicola, Megan -- Bottino, Rita -- Powers, Alvin C -- Harlan, David M -- Kent, Sally C -- Mannering, Stuart I -- Haskins, Kathryn -- 1K01DK094941/DK/NIDDK NIH HHS/ -- 1R01DK081166/DK/NIDDK NIH HHS/ -- 5U01DK89572/DK/NIDDK NIH HHS/ -- DK104211/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):711-4. doi: 10.1126/science.aad2791.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. thomas.delong@ucdenver.edu katie.haskins@ucdenver.edu. ; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. ; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. ; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA. ; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USA. ; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA. VA Tennessee Valley Healthcare System, Nashville, TN, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912858" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; C-Peptide/chemistry/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Clone Cells ; Diabetes Mellitus, Experimental/*immunology/pathology ; Diabetes Mellitus, Type 1/*immunology/pathology ; Epitopes/*immunology ; Immune Tolerance ; Insulin-Secreting Cells/*immunology/pathology ; Mice ; Mice, Inbred NOD ; Molecular Sequence Data ; Peptides/chemistry/immunology
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  • 6
    Publication Date: 2016-01-28
    Description: Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA-linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP)-activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toyama, Erin Quan -- Herzig, Sebastien -- Courchet, Julien -- Lewis, Tommy L Jr -- Loson, Oliver C -- Hellberg, Kristina -- Young, Nathan P -- Chen, Hsiuchen -- Polleux, Franck -- Chan, David C -- Shaw, Reuben J -- K99 NS091526/NS/NINDS NIH HHS/ -- K99NS091526/NS/NINDS NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01CA172229/CA/NCI NIH HHS/ -- R01DK080425/DK/NIDDK NIH HHS/ -- R01GM062967/GM/NIGMS NIH HHS/ -- R01GM110039/GM/NIGMS NIH HHS/ -- R01NS089456/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):275-81. doi: 10.1126/science.aab4138.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ; Department of Neuroscience, Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA. ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. ; Molecular and Cell Biology Laboratory and Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. shaw@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816379" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/chemistry/genetics/*metabolism ; Adenosine Monophosphate/metabolism ; Amino Acid Motifs ; Cell Line, Tumor ; Cytoplasm/enzymology ; Dactinomycin/analogs & derivatives/pharmacology ; *Energy Metabolism ; Enzyme Activation ; GTP Phosphohydrolases/genetics/metabolism ; Humans ; Microtubule-Associated Proteins/genetics/metabolism ; Mitochondria/drug effects/enzymology/*physiology ; *Mitochondrial Dynamics ; Mitochondrial Proteins/genetics/metabolism ; Molecular Sequence Data ; Rotenone/pharmacology ; *Stress, Physiological
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  • 7
    Publication Date: 2016-03-26
    Description: Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faria, Nuno Rodrigues -- Azevedo, Raimunda do Socorro da Silva -- Kraemer, Moritz U G -- Souza, Renato -- Cunha, Mariana Sequetin -- Hill, Sarah C -- Theze, Julien -- Bonsall, Michael B -- Bowden, Thomas A -- Rissanen, Ilona -- Rocco, Iray Maria -- Nogueira, Juliana Silva -- Maeda, Adriana Yurika -- Vasami, Fernanda Giseli da Silva -- Macedo, Fernando Luiz de Lima -- Suzuki, Akemi -- Rodrigues, Sueli Guerreiro -- Cruz, Ana Cecilia Ribeiro -- Nunes, Bruno Tardeli -- Medeiros, Daniele Barbosa de Almeida -- Rodrigues, Daniela Sueli Guerreiro -- Nunes Queiroz, Alice Louize -- da Silva, Eliana Vieira Pinto -- Henriques, Daniele Freitas -- Travassos da Rosa, Elisabeth Salbe -- de Oliveira, Consuelo Silva -- Martins, Livia Caricio -- Vasconcelos, Helena Baldez -- Casseb, Livia Medeiros Neves -- Simith, Darlene de Brito -- Messina, Jane P -- Abade, Leandro -- Lourenco, Jose -- Carlos Junior Alcantara, Luiz -- de Lima, Maricelia Maia -- Giovanetti, Marta -- Hay, Simon I -- de Oliveira, Rodrigo Santos -- Lemos, Poliana da Silva -- de Oliveira, Layanna Freitas -- de Lima, Clayton Pereira Silva -- da Silva, Sandro Patroca -- de Vasconcelos, Janaina Mota -- Franco, Luciano -- Cardoso, Jedson Ferreira -- Vianez-Junior, Joao Lidio da Silva Goncalves -- Mir, Daiana -- Bello, Gonzalo -- Delatorre, Edson -- Khan, Kamran -- Creatore, Marisa -- Coelho, Giovanini Evelim -- de Oliveira, Wanderson Kleber -- Tesh, Robert -- Pybus, Oliver G -- Nunes, Marcio R T -- Vasconcelos, Pedro F C -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 095066/Wellcome Trust/United Kingdom -- 102427/Wellcome Trust/United Kingdom -- MR/L009528/1/Medical Research Council/United Kingdom -- R24 AT 120942/AT/NCCIH NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):345-9. doi: 10.1126/science.aaf5036. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Para State, Brazil. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. ; Instituto Adolfo Lutz, University of Sao Paulo, Sao Paulo, Brazil. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. Metabiota, San Francisco, CA 94104, USA. ; Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil. ; Centre of Post Graduation in Collective Health, Department of Health, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil. ; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA 98121, USA. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. ; Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. ; Laboratorio de AIDS and Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. ; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Department of Medicine, Division of Infectious Diseases, University of Toronto, Toronto, Ontario, Canada. ; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. ; Brazilian Ministry of Health, Brasilia, Brazil. ; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. ; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK. Metabiota, San Francisco, CA 94104, USA. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br. ; Center for Technological Innovation, Evandro Chagas Institute, Ministry of Health, Ananindeua, PA 67030-000, Brazil. Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br. ; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Para State, Brazil. oliver.pybus@zoo.ox.ac.uk marcionunesbrasil@yahoo.com.br pedrovasconcelos@iec.pa.gov.br.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013429" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/virology ; Americas/epidemiology ; Animals ; *Disease Outbreaks ; Female ; Genome, Viral/genetics ; Humans ; Incidence ; Insect Vectors/virology ; Microcephaly/*epidemiology/virology ; Molecular Epidemiology ; Molecular Sequence Data ; Mutation ; Pacific Islands/epidemiology ; Phylogeny ; Pregnancy ; RNA, Viral/genetics ; Sequence Analysis, RNA ; Travel ; Zika Virus/classification/*genetics/isolation & purification ; Zika Virus Infection/*epidemiology/transmission/*virology
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  • 8
    Publication Date: 2016-03-12
    Description: Poly(ethylene terephthalate) (PET) is used extensively worldwide in plastic products, and its accumulation in the environment has become a global concern. Because the ability to enzymatically degrade PET has been thought to be limited to a few fungal species, biodegradation is not yet a viable remediation or recycling strategy. By screening natural microbial communities exposed to PET in the environment, we isolated a novel bacterium, Ideonella sakaiensis 201-F6, that is able to use PET as its major energy and carbon source. When grown on PET, this strain produces two enzymes capable of hydrolyzing PET and the reaction intermediate, mono(2-hydroxyethyl) terephthalic acid. Both enzymes are required to enzymatically convert PET efficiently into its two environmentally benign monomers, terephthalic acid and ethylene glycol.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoshida, Shosuke -- Hiraga, Kazumi -- Takehana, Toshihiko -- Taniguchi, Ikuo -- Yamaji, Hironao -- Maeda, Yasuhito -- Toyohara, Kiyotsuna -- Miyamoto, Kenji -- Kimura, Yoshiharu -- Oda, Kohei -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1196-9. doi: 10.1126/science.aad6359.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Biology, Faculty of Textile Science, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan. ; Department of Applied Biology, Faculty of Textile Science, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. ; Life Science Materials Laboratory, ADEKA, 7-2-34 Higashiogu, Arakawa-ku, Tokyo 116-8553, Japan. ; Department of Polymer Science, Faculty of Textile Science, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. ; Ecology-Related Material Group Innovation Research Institute, Teijin, Hinode-cho 2-1, Iwakuni, Yamaguchi 740-8511, Japan. ; Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965627" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Betaproteobacteria/*enzymology ; Environmental Restoration and Remediation ; Enzymes/classification/genetics/metabolism ; Hydrolysis ; Microbial Consortia ; Molecular Sequence Data ; Phthalic Acids/metabolism ; Phylogeny ; Plastics/*metabolism ; Polyethylene Terephthalates/*metabolism ; Recycling
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  • 9
    Publication Date: 2016-02-06
    Description: SH3 and multiple ankyrin repeat domains 3 (SHANK3) haploinsufficiency is causative for the neurological features of Phelan-McDermid syndrome (PMDS), including a high risk of autism spectrum disorder (ASD). We used unbiased, quantitative proteomics to identify changes in the phosphoproteome of Shank3-deficient neurons. Down-regulation of protein kinase B (PKB/Akt)-mammalian target of rapamycin complex 1 (mTORC1) signaling resulted from enhanced phosphorylation and activation of serine/threonine protein phosphatase 2A (PP2A) regulatory subunit, B56beta, due to increased steady-state levels of its kinase, Cdc2-like kinase 2 (CLK2). Pharmacological and genetic activation of Akt or inhibition of CLK2 relieved synaptic deficits in Shank3-deficient and PMDS patient-derived neurons. CLK2 inhibition also restored normal sociability in a Shank3-deficient mouse model. Our study thereby provides a novel mechanistic and potentially therapeutic understanding of deregulated signaling downstream of Shank3 deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bidinosti, Michael -- Botta, Paolo -- Kruttner, Sebastian -- Proenca, Catia C -- Stoehr, Natacha -- Bernhard, Mario -- Fruh, Isabelle -- Mueller, Matthias -- Bonenfant, Debora -- Voshol, Hans -- Carbone, Walter -- Neal, Sarah J -- McTighe, Stephanie M -- Roma, Guglielmo -- Dolmetsch, Ricardo E -- Porter, Jeffrey A -- Caroni, Pico -- Bouwmeester, Tewis -- Luthi, Andreas -- Galimberti, Ivan -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1199-203. doi: 10.1126/science.aad5487. Epub 2016 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Friedrich Miescher Institute, Basel, Switzerland. ; Analytical Sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Neuroscience, Novartis Institutes for Biomedical Research, Cambridge, USA. ; Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ivan.galimberti@novartis.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26847545" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Autism Spectrum Disorder/*drug therapy/enzymology/genetics ; Chromosome Deletion ; Chromosome Disorders/genetics ; Chromosomes, Human, Pair 22/genetics ; Disease Models, Animal ; Down-Regulation ; Gene Knockdown Techniques ; Humans ; Insulin-Like Growth Factor I/metabolism ; Mice ; Molecular Sequence Data ; Multiprotein Complexes/metabolism ; Nerve Tissue Proteins/*genetics ; Neurons/enzymology ; Phosphorylation ; Protein Phosphatase 2/metabolism ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Proteomics ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; Rats ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
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  • 10
    Publication Date: 2016-03-26
    Description: Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naive B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naive B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872700/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph G -- Kulp, Daniel W -- Havenar-Daughton, Colin -- Sarkar, Anita -- Briney, Bryan -- Sok, Devin -- Sesterhenn, Fabian -- Ereno-Orbea, June -- Kalyuzhniy, Oleksandr -- Deresa, Isaiah -- Hu, Xiaozhen -- Spencer, Skye -- Jones, Meaghan -- Georgeson, Erik -- Adachi, Yumiko -- Kubitz, Michael -- deCamp, Allan C -- Julien, Jean-Philippe -- Wilson, Ian A -- Burton, Dennis R -- Crotty, Shane -- Schief, William R -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI110657/AI/NIAID NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1458-63. doi: 10.1126/science.aad9195.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Vaccine and Infectious Disease Division, Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. Departments of Biochemistry and Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA. schief@scripps.edu shane@lji.org. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. schief@scripps.edu shane@lji.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013733" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Amino Acid Sequence ; Antibodies, Monoclonal/chemistry/*immunology/isolation & purification ; Antibodies, Neutralizing/chemistry/*immunology/isolation & purification ; Antibody Affinity ; B-Lymphocytes/immunology ; Cell Separation ; Combinatorial Chemistry Techniques ; Epitopes, B-Lymphocyte/chemistry/genetics/*immunology ; Germ Cells/*immunology ; HIV Antibodies/chemistry/*immunology/isolation & purification ; HIV-1/*immunology ; Humans ; Molecular Sequence Data ; Mutation ; Peptide Library ; Precursor Cells, B-Lymphoid/*immunology ; Protein Conformation
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  • 11
    Publication Date: 2016-04-02
    Description: Recent studies have implicated long noncoding RNAs (lncRNAs) as regulators of many important biological processes. Here we report on the identification and characterization of a lncRNA, lnc13, that harbors a celiac disease-associated haplotype block and represses expression of certain inflammatory genes under homeostatic conditions. Lnc13 regulates gene expression by binding to hnRNPD, a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). Upon stimulation, lnc13 levels are reduced, thereby allowing increased expression of the repressed genes. Lnc13 levels are significantly decreased in small intestinal biopsy samples from patients with celiac disease, which suggests that down-regulation of lnc13 may contribute to the inflammation seen in this disease. Furthermore, the lnc13 disease-associated variant binds hnRNPD less efficiently than its wild-type counterpart, thus helping to explain how these single-nucleotide polymorphisms contribute to celiac disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castellanos-Rubio, Ainara -- Fernandez-Jimenez, Nora -- Kratchmarov, Radomir -- Luo, Xiaobing -- Bhagat, Govind -- Green, Peter H R -- Schneider, Robert -- Kiledjian, Megerditch -- Bilbao, Jose Ramon -- Ghosh, Sankar -- R01-AI093985/AI/NIAID NIH HHS/ -- R01-DK102180/DK/NIDDK NIH HHS/ -- R01-GM067005/GM/NIGMS NIH HHS/ -- R37-AI33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):91-5. doi: 10.1126/science.aad0467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country (UPV-EHU), BioCruces Research Institute, Leioa 48940, Basque Country, Spain. ; Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Center for Celiac Disease, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. ; Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. sg2715@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034373" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Celiac Disease/*genetics/pathology ; Down-Regulation ; Gene Expression Regulation ; *Genetic Predisposition to Disease ; Haplotypes ; Heterogeneous-Nuclear Ribonucleoproteins/genetics ; Humans ; Inflammation/*genetics ; Mice ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/*genetics
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  • 12
    Publication Date: 2016-02-26
    Description: The oxidation of methane with sulfate is an important microbial metabolism in the global carbon cycle. In marine methane seeps, this process is mediated by consortia of anaerobic methanotrophic archaea (ANME) that live in syntrophy with sulfate-reducing bacteria (SRB). The underlying interdependencies within this uncultured symbiotic partnership are poorly understood. We used a combination of rate measurements and single-cell stable isotope probing to demonstrate that ANME in deep-sea sediments can be catabolically and anabolically decoupled from their syntrophic SRB partners using soluble artificial oxidants. The ANME still sustain high rates of methane oxidation in the absence of sulfate as the terminal oxidant, lending support to the hypothesis that interspecies extracellular electron transfer is the syntrophic mechanism for the anaerobic oxidation of methane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheller, Silvan -- Yu, Hang -- Chadwick, Grayson L -- McGlynn, Shawn E -- Orphan, Victoria J -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):703-7. doi: 10.1126/science.aad7154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912857" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; *Carbon Cycle ; Electron Transport ; Geologic Sediments/microbiology ; Methane/*metabolism ; Methanosarcinales/classification/genetics/*metabolism ; Molecular Sequence Data ; Oxidation-Reduction ; Phylogeny ; RNA, Archaeal/classification/genetics ; Seawater/microbiology ; Sulfates/*metabolism ; Sulfur-Reducing Bacteria/metabolism
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  • 13
    Publication Date: 2015-05-23
    Description: Sex determination in the mosquito Aedes aegypti is governed by a dominant male-determining factor (M factor) located within a Y chromosome-like region called the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two characteristics required of an M factor. Nix knockout with clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 resulted in largely feminized genetic males and the production of female isoforms of two key regulators of sexual differentiation: doublesex and fruitless. Ectopic expression of Nix resulted in genetic females with nearly complete male genitalia. Thus, Nix is both required and sufficient to initiate male development. This study provides a foundation for mosquito control strategies that convert female mosquitoes into harmless males.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hall, Andrew Brantley -- Basu, Sanjay -- Jiang, Xiaofang -- Qi, Yumin -- Timoshevskiy, Vladimir A -- Biedler, James K -- Sharakhova, Maria V -- Elahi, Rubayet -- Anderson, Michelle A E -- Chen, Xiao-Guang -- Sharakhov, Igor V -- Adelman, Zach N -- Tu, Zhijian -- AI113643/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1268-70. doi: 10.1126/science.aaa2850. Epub 2015 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. ; Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. ; Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. ; Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. ; School of Public Health and Tropical Medicine, Southern Medical University, Guangdong, People's Republic of China. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. Department of Entomology, Virginia Tech, Blacksburg, VA, USA. jaketu@vt.edu zachadel@vt.edu. ; Interdisciplinary PhD Program in Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA. Fralin Life Science Institute, Virginia Tech, Blacksburg, VA, USA. jaketu@vt.edu zachadel@vt.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999371" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/*genetics/*growth & development ; Animals ; Caspase 9 ; Clustered Regularly Interspaced Short Palindromic Repeats ; Female ; Gene Knockout Techniques ; *Genes, Insect ; *Genetic Loci ; Male ; Molecular Sequence Data ; Mosquito Control/methods ; Sex Determination Processes/*genetics
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  • 14
    Publication Date: 2015-05-23
    Description: Extremophiles, microorganisms thriving in extreme environmental conditions, must have proteins and nucleic acids that are stable at extremes of temperature and pH. The nonenveloped, rod-shaped virus SIRV2 (Sulfolobus islandicus rod-shaped virus 2) infects the hyperthermophilic acidophile Sulfolobus islandicus, which lives at 80 degrees C and pH 3. We have used cryo-electron microscopy to generate a three-dimensional reconstruction of the SIRV2 virion at ~4 angstrom resolution, which revealed a previously unknown form of virion organization. Although almost half of the capsid protein is unstructured in solution, this unstructured region folds in the virion into a single extended alpha helix that wraps around the DNA. The DNA is entirely in the A-form, which suggests a common mechanism with bacterial spores for protecting DNA in the most adverse environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiMaio, Frank -- Yu, Xiong -- Rensen, Elena -- Krupovic, Mart -- Prangishvili, David -- Egelman, Edward H -- GM035269/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):914-7. doi: 10.1126/science.aaa4181.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. ; Institut Pasteur, Department of Microbiology, 25 rue du Dr. Roux, Paris 75015, France. ; Institut Pasteur, Department of Microbiology, 25 rue du Dr. Roux, Paris 75015, France. egelman@virginia.edu david.prangishvili@pasteur.fr. ; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA. egelman@virginia.edu david.prangishvili@pasteur.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999507" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cryoelectron Microscopy ; DNA, A-Form/*metabolism ; Molecular Sequence Data ; Protein Multimerization ; Protein Structure, Secondary ; Rudiviridae/*metabolism/ultrastructure ; Spores, Bacterial/genetics/virology ; Sulfolobus/*genetics/*virology ; Virion/*ultrastructure
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  • 15
    Publication Date: 2015-10-10
    Description: Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toh, Shigeo -- Holbrook-Smith, Duncan -- Stogios, Peter J -- Onopriyenko, Olena -- Lumba, Shelley -- Tsuchiya, Yuichiro -- Savchenko, Alexei -- McCourt, Peter -- New York, N.Y. -- Science. 2015 Oct 9;350(6257):203-7. doi: 10.1126/science.aac9476.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto M5S 3B2, Canada. ; Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, 200 College Street, Toronto M5S 3E5, Canada. Center for Structural Genomics of Infectious Diseases, contracted by National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, 200 College Street, Toronto M5S 3E5, Canada. ; Institute of Transformative Bio-Molecules, Nagoya University, Japan, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan. ; Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto M5S 3B2, Canada. peter.mccourt@utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26450211" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/metabolism ; Catalytic Domain ; Germination/drug effects ; Heterocyclic Compounds, 3-Ring/*metabolism/pharmacology ; Lactones/*metabolism/pharmacology ; Molecular Sequence Data ; Phylogeny ; Plant Growth Regulators/*metabolism/pharmacology ; Plant Proteins/*chemistry/classification/genetics ; Protein Structure, Secondary ; Receptors, Cell Surface/*chemistry/classification/genetics ; Seeds/genetics/growth & development/metabolism ; Striga/genetics/growth & development/*metabolism ; Structure-Activity Relationship
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  • 16
    Publication Date: 2015-03-15
    Description: TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Yin Yao -- Pike, Ashley C W -- Mackenzie, Alexandra -- McClenaghan, Conor -- Aryal, Prafulla -- Dong, Liang -- Quigley, Andrew -- Grieben, Mariana -- Goubin, Solenne -- Mukhopadhyay, Shubhashish -- Ruda, Gian Filippo -- Clausen, Michael V -- Cao, Lishuang -- Brennan, Paul E -- Burgess-Brown, Nicola A -- Sansom, Mark S P -- Tucker, Stephen J -- Carpenter, Elisabeth P -- 084655/Wellcome Trust/United Kingdom -- 092809/Z/10/Z/Wellcome Trust/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1256-9. doi: 10.1126/science.1261512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. ; Pfizer Neusentis, Granta Park, Cambridge CB21 6GS, UK. ; OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. ; Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk. ; Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. OXION Initiative in Ion Channels and Disease, University of Oxford, Oxford OX1 3PN, UK. liz.carpenter@sgc.ox.ac.uk stephen.tucker@physics.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766236" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arachidonic Acid/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Fluoxetine/analogs & derivatives/chemistry/metabolism/pharmacology ; Humans ; *Ion Channel Gating ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Potassium/metabolism ; Potassium Channels, Tandem Pore Domain/antagonists & ; inhibitors/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 17
    Publication Date: 2015-11-07
    Description: Understanding the evolution of sex determination in plants requires identifying the mechanisms underlying the transition from monoecious plants, where male and female flowers coexist, to unisexual individuals found in dioecious species. We show that in melon and cucumber, the androecy gene controls female flower development and encodes a limiting enzyme of ethylene biosynthesis, ACS11. ACS11 is expressed in phloem cells connected to flowers programmed to become female, and ACS11 loss-of-function mutants lead to male plants (androecy). CmACS11 represses the expression of the male promoting gene CmWIP1 to control the development and the coexistence of male and female flowers in monoecious species. Because monoecy can lead to dioecy, we show how a combination of alleles of CmACS11 and CmWIP1 can create artificial dioecy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boualem, Adnane -- Troadec, Christelle -- Camps, Celine -- Lemhemdi, Afef -- Morin, Halima -- Sari, Marie-Agnes -- Fraenkel-Zagouri, Rina -- Kovalski, Irina -- Dogimont, Catherine -- Perl-Treves, Rafael -- Bendahmane, Abdelhafid -- New York, N.Y. -- Science. 2015 Nov 6;350(6261):688-91. doi: 10.1126/science.aac8370.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut National de la Recherche Agronomique (INRA), Institute of Plant Sciences Paris-Saclay, CNRS, Universite Paris-Sud, Universite d'Evry, Universite Paris-Diderot, Batiment 630, 91405, Orsay, France. ; Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS, UMR 8601, Universite Rene Descartes, Paris, France. ; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. ; INRA, UR 1052, Unite de Genetique et d'Amelioration des Fruits et Legumes, BP 94, F-84143 Montfavet, France. ; Institut National de la Recherche Agronomique (INRA), Institute of Plant Sciences Paris-Saclay, CNRS, Universite Paris-Sud, Universite d'Evry, Universite Paris-Diderot, Batiment 630, 91405, Orsay, France. bendahm@evry.inra.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26542573" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; *Biological Evolution ; Cucumis sativus/enzymology/genetics/growth & development ; Cucurbitaceae/enzymology/genetics/*growth & development ; Ethylenes/biosynthesis ; Flowers/enzymology/genetics/*growth & development ; Genes, Plant/genetics/physiology ; Lyases/genetics/*physiology ; Molecular Sequence Data ; Phloem/enzymology/genetics/growth & development ; Plant Proteins/genetics/*physiology ; Sex Determination Processes/*genetics
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  • 18
    Publication Date: 2015-08-22
    Description: Elucidating the signaling mechanism of strigolactones has been the key to controlling the devastating problem caused by the parasitic plant Striga hermonthica. To overcome the genetic intractability that has previously interfered with identification of the strigolactone receptor, we developed a fluorescence turn-on probe, Yoshimulactone Green (YLG), which activates strigolactone signaling and illuminates signal perception by the strigolactone receptors. Here we describe how strigolactones bind to and act via ShHTLs, the diverged family of alpha/beta hydrolase-fold proteins in Striga. Live imaging using YLGs revealed that a dynamic wavelike propagation of strigolactone perception wakes up Striga seeds. We conclude that ShHTLs function as the strigolactone receptors mediating seed germination in Striga. Our findings enable access to strigolactone receptors and observation of the regulatory dynamics for strigolactone signal transduction in Striga.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchiya, Yuichiro -- Yoshimura, Masahiko -- Sato, Yoshikatsu -- Kuwata, Keiko -- Toh, Shigeo -- Holbrook-Smith, Duncan -- Zhang, Hua -- McCourt, Peter -- Itami, Kenichiro -- Kinoshita, Toshinori -- Hagihara, Shinya -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):864-8. doi: 10.1126/science.aab3831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Department of Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, Ontario M5S 3B2, Canada. yuichiro@itbm.nagoya-u.ac.jp hagi@itbm.nagoya-u.ac.jp. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Department of Cell and Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, Ontario M5S 3B2, Canada. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Japan Science and Technology Agency-Exploratory Research for Advanced Technology, Itami Molecular Nanocarbon Project, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. ; Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan. yuichiro@itbm.nagoya-u.ac.jp hagi@itbm.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293962" target="_blank"〉PubMed〈/a〉
    Keywords: Fluoresceins/chemistry/metabolism ; Fluorescence ; Fluorescent Dyes/chemistry/metabolism ; *Germination ; Hydrolases/metabolism ; Hydrolysis ; Lactones/*metabolism ; Molecular Imaging/methods ; Molecular Sequence Data ; Plant Growth Regulators/*metabolism ; Plant Proteins/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Seeds/*growth & development/metabolism ; Signal Transduction ; Striga/*growth & development/metabolism
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  • 19
    Publication Date: 2015-09-26
    Description: Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) detects intracellular DNA and signals through the adapter protein STING to initiate the antiviral response to DNA viruses. Whether DNA viruses can prevent activation of the cGAS-STING pathway remains largely unknown. Here, we identify the oncogenes of the DNA tumor viruses, including E7 from human papillomavirus (HPV) and E1A from adenovirus, as potent and specific inhibitors of the cGAS-STING pathway. We show that the LXCXE motif of these oncoproteins, which is essential for blockade of the retinoblastoma tumor suppressor, is also important for antagonizing DNA sensing. E1A and E7 bind to STING, and silencing of these oncogenes in human tumor cells restores the cGAS-STING pathway. Our findings reveal a host-virus conflict that may have shaped the evolution of viral oncogenes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lau, Laura -- Gray, Elizabeth E -- Brunette, Rebecca L -- Stetson, Daniel B -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):568-71. doi: 10.1126/science.aab3291. Epub 2015 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. ; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. stetson@uw.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26405230" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/chemistry/genetics/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; DNA Tumor Viruses/*immunology ; DNA, Neoplasm/immunology ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Evolution, Molecular ; HEK293 Cells ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Membrane Proteins/*antagonists & inhibitors ; Metabolic Networks and Pathways ; Molecular Sequence Data ; Nucleotides, Cyclic/*antagonists & inhibitors ; Oncogene Proteins, Viral/chemistry/genetics/*metabolism ; Retinoblastoma Protein/antagonists & inhibitors ; *Tumor Escape
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  • 20
    Publication Date: 2015-09-12
    Description: Podophyllotoxin is the natural product precursor of the chemotherapeutic etoposide, yet only part of its biosynthetic pathway is known. We used transcriptome mining in Podophyllum hexandrum (mayapple) to identify biosynthetic genes in the podophyllotoxin pathway. We selected 29 candidate genes to combinatorially express in Nicotiana benthamiana (tobacco) and identified six pathway enzymes, including an oxoglutarate-dependent dioxygenase that closes the core cyclohexane ring of the aryltetralin scaffold. By coexpressing 10 genes in tobacco-these 6 plus 4 previously discovered-we reconstitute the pathway to (-)-4'-desmethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Our results enable production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lau, Warren -- Sattely, Elizabeth S -- DP2 AT008321/AT/NCCIH NIH HHS/ -- R00 GM089985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1224-8. doi: 10.1126/science.aac7202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA. sattely@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26359402" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biosynthetic Pathways/genetics ; Etoposide/*metabolism ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; *Genetic Engineering ; Methylation ; Mixed Function Oxygenases/genetics/*metabolism ; Molecular Sequence Data ; Podophyllotoxin/*analogs & derivatives/biosynthesis/*metabolism ; Podophyllum peltatum/*enzymology/genetics ; Tobacco/genetics/*metabolism ; Topoisomerase Inhibitors/*metabolism ; Transcriptome
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  • 21
    Publication Date: 2015-03-31
    Description: The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 x 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoenen, T -- Safronetz, D -- Groseth, A -- Wollenberg, K R -- Koita, O A -- Diarra, B -- Fall, I S -- Haidara, F C -- Diallo, F -- Sanogo, M -- Sarro, Y S -- Kone, A -- Togo, A C G -- Traore, A -- Kodio, M -- Dosseh, A -- Rosenke, K -- de Wit, E -- Feldmann, F -- Ebihara, H -- Munster, V J -- Zoon, K C -- Feldmann, H -- Sow, S -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):117-9. doi: 10.1126/science.aaa5646. Epub 2015 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. ; Bioinformatics and Computational Biosciences Branch, NIAID, NIH, Bethesda, MD 20892, USA. ; Center of Research and Training for HIV and Tuberculosis, University of Science, Technique and Technologies of Bamako, Mali. ; World Health Organization Office, Bamako, Mali. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. ; World Health Organization Inter-Country Support Team, Ouagadougou, Burkina Faso. ; Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA. ; Office of the Scientific Director, NIAID, NIH, Bethesda, MD 20895, USA. ; Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814067" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Disease Outbreaks ; Ebolavirus/classification/*genetics/isolation & purification ; Genotype ; Hemorrhagic Fever, Ebola/epidemiology/*virology ; Humans ; Mali/epidemiology ; Molecular Sequence Data ; *Mutation Rate ; Phylogeny
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  • 22
    Publication Date: 2015-09-01
    Description: DNA strand exchange plays a central role in genetic recombination across all kingdoms of life, but the physical basis for these reactions remains poorly defined. Using single-molecule imaging, we found that bacterial RecA and eukaryotic Rad51 and Dmc1 all stabilize strand exchange intermediates in precise three-nucleotide steps. Each step coincides with an energetic signature (0.3 kBT) that is conserved from bacteria to humans. Triplet recognition is strictly dependent on correct Watson-Crick pairing. Rad51, RecA, and Dmc1 can all step over mismatches, but only Dmc1 can stabilize mismatched triplets. This finding provides insight into why eukaryotes have evolved a meiosis-specific recombinase. We propose that canonical Watson-Crick base triplets serve as the fundamental unit of pairing interactions during DNA recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580133/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Ja Yil -- Terakawa, Tsuyoshi -- Qi, Zhi -- Steinfeld, Justin B -- Redding, Sy -- Kwon, YoungHo -- Gaines, William A -- Zhao, Weixing -- Sung, Patrick -- Greene, Eric C -- CA146940/CA/NCI NIH HHS/ -- GM074739/GM/NIGMS NIH HHS/ -- R01 CA146940/CA/NCI NIH HHS/ -- R01 ES015252/ES/NIEHS NIH HHS/ -- R01 GM074739/GM/NIGMS NIH HHS/ -- R01ES015252/ES/NIEHS NIH HHS/ -- T32 GM007367/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):977-81. doi: 10.1126/science.aab2666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Department of Biophysics, Kyoto University, Sakyo, Kyoto, Japan. ; Department of Chemistry, Columbia University, New York, NY, USA. ; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Howard Hughes Medical Institute, Columbia University, New York, NY, USA. ecg2108@cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315438" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Pairing ; Base Sequence ; Cell Cycle Proteins/chemistry/metabolism ; DNA/*chemistry/*metabolism ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Escherichia coli Proteins/chemistry/metabolism ; Evolution, Molecular ; *Homologous Recombination ; Humans ; Meiosis ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Rad51 Recombinase/chemistry/*metabolism ; Rec A Recombinases/chemistry/*metabolism ; Recombinases/chemistry/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Thermodynamics
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  • 23
    Publication Date: 2015-01-03
    Description: Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380271/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neafsey, Daniel E -- Waterhouse, Robert M -- Abai, Mohammad R -- Aganezov, Sergey S -- Alekseyev, Max A -- Allen, James E -- Amon, James -- Arca, Bruno -- Arensburger, Peter -- Artemov, Gleb -- Assour, Lauren A -- Basseri, Hamidreza -- Berlin, Aaron -- Birren, Bruce W -- Blandin, Stephanie A -- Brockman, Andrew I -- Burkot, Thomas R -- Burt, Austin -- Chan, Clara S -- Chauve, Cedric -- Chiu, Joanna C -- Christensen, Mikkel -- Costantini, Carlo -- Davidson, Victoria L M -- Deligianni, Elena -- Dottorini, Tania -- Dritsou, Vicky -- Gabriel, Stacey B -- Guelbeogo, Wamdaogo M -- Hall, Andrew B -- Han, Mira V -- Hlaing, Thaung -- Hughes, Daniel S T -- Jenkins, Adam M -- Jiang, Xiaofang -- Jungreis, Irwin -- Kakani, Evdoxia G -- Kamali, Maryam -- Kemppainen, Petri -- Kennedy, Ryan C -- Kirmitzoglou, Ioannis K -- Koekemoer, Lizette L -- Laban, Njoroge -- Langridge, Nicholas -- Lawniczak, Mara K N -- Lirakis, Manolis -- Lobo, Neil F -- Lowy, Ernesto -- MacCallum, Robert M -- Mao, Chunhong -- Maslen, Gareth -- Mbogo, Charles -- McCarthy, Jenny -- Michel, Kristin -- Mitchell, Sara N -- Moore, Wendy -- Murphy, Katherine A -- Naumenko, Anastasia N -- Nolan, Tony -- Novoa, Eva M -- O'Loughlin, Samantha -- Oringanje, Chioma -- Oshaghi, Mohammad A -- Pakpour, Nazzy -- Papathanos, Philippos A -- Peery, Ashley N -- Povelones, Michael -- Prakash, Anil -- Price, David P -- Rajaraman, Ashok -- Reimer, Lisa J -- Rinker, David C -- Rokas, Antonis -- Russell, Tanya L -- Sagnon, N'Fale -- Sharakhova, Maria V -- Shea, Terrance -- Simao, Felipe A -- Simard, Frederic -- Slotman, Michel A -- Somboon, Pradya -- Stegniy, Vladimir -- Struchiner, Claudio J -- Thomas, Gregg W C -- Tojo, Marta -- Topalis, Pantelis -- Tubio, Jose M C -- Unger, Maria F -- Vontas, John -- Walton, Catherine -- Wilding, Craig S -- Willis, Judith H -- Wu, Yi-Chieh -- Yan, Guiyun -- Zdobnov, Evgeny M -- Zhou, Xiaofan -- Catteruccia, Flaminia -- Christophides, George K -- Collins, Frank H -- Cornman, Robert S -- Crisanti, Andrea -- Donnelly, Martin J -- Emrich, Scott J -- Fontaine, Michael C -- Gelbart, William -- Hahn, Matthew W -- Hansen, Immo A -- Howell, Paul I -- Kafatos, Fotis C -- Kellis, Manolis -- Lawson, Daniel -- Louis, Christos -- Luckhart, Shirley -- Muskavitch, Marc A T -- Ribeiro, Jose M -- Riehle, Michael A -- Sharakhov, Igor V -- Tu, Zhijian -- Zwiebel, Laurence J -- Besansky, Nora J -- 092654/Wellcome Trust/United Kingdom -- R01 AI050243/AI/NIAID NIH HHS/ -- R01 AI063508/AI/NIAID NIH HHS/ -- R01 AI073745/AI/NIAID NIH HHS/ -- R01 AI076584/AI/NIAID NIH HHS/ -- R01 AI080799/AI/NIAID NIH HHS/ -- R01 AI104956/AI/NIAID NIH HHS/ -- R21 AI101459/AI/NIAID NIH HHS/ -- R56 AI107263/AI/NIAID NIH HHS/ -- SC1 AI109055/AI/NIAID NIH HHS/ -- U19 AI089686/AI/NIAID NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U41 HG007234/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):1258522. doi: 10.1126/science.1258522. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. neafsey@broadinstitute.org nbesansk@nd.edu. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Medical Entomology and Vector Control, School of Public Health and Institute of Health Researches, Tehran University of Medical Sciences, Tehran, Iran. ; George Washington University, Department of Mathematics and Computational Biology Institute, 45085 University Drive, Ashburn, VA 20147, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; National Vector Borne Disease Control Programme, Ministry of Health, Tafea Province, Vanuatu. ; Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. ; Department of Biological Sciences, California State Polytechnic-Pomona, 3801 West Temple Avenue, Pomona, CA 91768, USA. ; Tomsk State University, 36 Lenina Avenue, Tomsk, Russia. ; Department of Computer Science and Engineering, Eck Institute for Global Health, 211B Cushing Hall, University of Notre Dame, Notre Dame, IN 46556, USA. ; Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Inserm, U963, F-67084 Strasbourg, France. CNRS, UPR9022, IBMC, F-67084 Strasbourg, France. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. ; Faculty of Medicine, Health and Molecular Science, Australian Institute of Tropical Health Medicine, James Cook University, Cairns 4870, Australia. ; Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. ; Department of Mathematics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. ; Department of Entomology and Nematology, One Shields Avenue, University of California-Davis, Davis, CA 95616, USA. ; Institut de Recherche pour le Developpement, Unites Mixtes de Recherche Maladies Infectieuses et Vecteurs Ecologie, Genetique, Evolution et Controle, 911, Avenue Agropolis, BP 64501 Montpellier, France. ; Division of Biology, Kansas State University, 271 Chalmers Hall, Manhattan, KS 66506, USA. ; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. ; Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Genomics Platform, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou 01 BP 2208, Burkina Faso. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; School of Life Sciences, University of Nevada, Las Vegas, NV 89154, USA. ; Department of Medical Research, No. 5 Ziwaka Road, Dagon Township, Yangon 11191, Myanmar. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. ; Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita degli Studi di Perugia, Perugia, Italy. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Computational Evolutionary Biology Group, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Bioinformatics Research Laboratory, Department of Biological Sciences, New Campus, University of Cyprus, CY 1678 Nicosia, Cyprus. ; Wits Research Institute for Malaria, Faculty of Health Sciences, and Vector Control Reference Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, Johannesburg, South Africa. ; National Museums of Kenya, P.O. Box 40658-00100, Nairobi, Kenya. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. ; Virginia Bioinformatics Institute, 1015 Life Science Circle, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, P.O. Box 230-80108, Kilifi, Kenya. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. ; Department of Entomology, 1140 East South Campus Drive, Forbes 410, University of Arizona, Tucson, AZ 85721, USA. ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, One Shields Avenue, Davis, CA 95616, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA. ; Regional Medical Research Centre NE, Indian Council of Medical Research, P.O. Box 105, Dibrugarh-786 001, Assam, India. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Entomology, Texas A&M University, College Station, TX 77807, USA. ; Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. ; Fundacao Oswaldo Cruz, Avenida Brasil 4365, RJ Brazil. Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. ; School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Department of Physiology, School of Medicine, Center for Research in Molecular Medicine and Chronic Diseases, Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Santiago de Compostela, A Coruna, Spain. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK. ; School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, UK. ; Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Computer Science, Harvey Mudd College, Claremont, CA 91711, USA. ; Program in Public Health, College of Health Sciences, University of California, Irvine, Hewitt Hall, Irvine, CA 92697, USA. ; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SJ, UK. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. Centre of Evolutionary and Ecological Studies (Marine Evolution and Conservation group), University of Groningen, Nijenborgh 7, NL-9747 AG Groningen, Netherlands. ; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. ; Department of Biology, Indiana University, Bloomington, IN 47405, USA. School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Centers for Disease Control and Prevention, 1600 Clifton Road NE MSG49, Atlanta, GA 30329, USA. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, 12735 Twinbrook Parkway, Rockville, MD 20852, USA. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Departments of Biological Sciences and Pharmacology, Institutes for Chemical Biology, Genetics and Global Health, Vanderbilt University and Medical Center, Nashville, TN 37235, USA. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. neafsey@broadinstitute.org nbesansk@nd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554792" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/classification/*genetics ; Base Sequence ; Chromosomes, Insect/genetics ; Drosophila/genetics ; *Evolution, Molecular ; *Genome, Insect ; Humans ; Insect Vectors/classification/*genetics ; Malaria/*transmission ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 24
    Publication Date: 2015-10-17
    Description: Transcriptional enhancers direct precise on-off patterns of gene expression during development. To explore the basis for this precision, we conducted a high-throughput analysis of the Otx-a enhancer, which mediates expression in the neural plate of Ciona embryos in response to fibroblast growth factor (FGF) signaling and a localized GATA determinant. We provide evidence that enhancer specificity depends on submaximal recognition motifs having reduced binding affinities ("suboptimization"). Native GATA and ETS (FGF) binding sites contain imperfect matches to consensus motifs. Perfect matches mediate robust but ectopic patterns of gene expression. The native sites are not arranged at optimal intervals, and subtle changes in their spacing alter enhancer activity. Multiple tiers of enhancer suboptimization produce specific, but weak, patterns of expression, and we suggest that clusters of weak enhancers, including certain "superenhancers," circumvent this trade-off in specificity and activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farley, Emma K -- Olson, Katrina M -- Zhang, Wei -- Brandt, Alexander J -- Rokhsar, Daniel S -- Levine, Michael S -- GM46638/GM/NIGMS NIH HHS/ -- NS076542/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):325-8. doi: 10.1126/science.aac6948.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. msl2@princeton.edu ekfarley@princeton.edu. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. ; Department of Medicine, University of California, San Diego, CA 92093-0688, USA. ; Department of Chemistry, University of California, Berkeley, CA 94720-3200, USA. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472909" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Ciona intestinalis/genetics/*growth & development ; Consensus Sequence ; Enhancer Elements, Genetic/genetics/*physiology ; Fas-Associated Death Domain Protein/metabolism ; Fibroblast Growth Factors/*metabolism ; GATA Transcription Factors/*metabolism ; *Gene Expression Regulation, Developmental ; Molecular Sequence Data ; Organ Specificity/genetics/physiology ; Otx Transcription Factors/*metabolism
    Print ISSN: 0036-8075
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  • 25
    Publication Date: 2015-01-13
    Description: NADPH/NADP(+) (the reduced form of NADP(+)/nicotinamide adenine dinucleotide phosphate) homeostasis is critical for countering oxidative stress in cells. Nicotinamide nucleotide transhydrogenase (TH), a membrane enzyme present in both bacteria and mitochondria, couples the proton motive force to the generation of NADPH. We present the 2.8 A crystal structure of the transmembrane proton channel domain of TH from Thermus thermophilus and the 6.9 A crystal structure of the entire enzyme (holo-TH). The membrane domain crystallized as a symmetric dimer, with each protomer containing a putative proton channel. The holo-TH is a highly asymmetric dimer with the NADP(H)-binding domain (dIII) in two different orientations. This unusual arrangement suggests a catalytic mechanism in which the two copies of dIII alternatively function in proton translocation and hydride transfer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479213/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479213/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leung, Josephine H -- Schurig-Briccio, Lici A -- Yamaguchi, Mutsuo -- Moeller, Arne -- Speir, Jeffrey A -- Gennis, Robert B -- Stout, Charles D -- 1R01GM103838-01A1/GM/NIGMS NIH HHS/ -- 5R01GM061545/GM/NIGMS NIH HHS/ -- GM073197/GM/NIGMS NIH HHS/ -- GM095600/GM/NIGMS NIH HHS/ -- P41 GM103310/GM/NIGMS NIH HHS/ -- P41GM103310/GM/NIGMS NIH HHS/ -- R01 GM061545/GM/NIGMS NIH HHS/ -- R01 GM095600/GM/NIGMS NIH HHS/ -- R01 GM103838/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):178-81. doi: 10.1126/science.1260451.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA. ; National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. dave@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25574024" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Molecular Sequence Data ; NADP Transhydrogenases/*chemistry ; Protein Multimerization ; Protein Structure, Tertiary ; *Protons ; Thermus thermophilus/enzymology
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  • 26
    Publication Date: 2015-07-15
    Description: The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nie, Yonggang -- Speakman, John R -- Wu, Qi -- Zhang, Chenglin -- Hu, Yibo -- Xia, Maohua -- Yan, Li -- Hambly, Catherine -- Wang, Lu -- Wei, Wei -- Zhang, Jinguo -- Wei, Fuwen -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):171-4. doi: 10.1126/science.aab2413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; Beijing Key Laboratory of Captive Wildlife Technologies, Beijing Zoo, Beijing, China. ; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. ; Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. weifw@ioz.ac.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160943" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Body Temperature ; Cattle ; Chromosomes, Human, Pair 15/genetics ; Diet/veterinary ; Dogs ; *Eating ; Energy Metabolism/genetics/*physiology ; Gastrointestinal Tract ; Genetic Variation ; Humans ; Mice ; Molecular Sequence Data ; Motor Activity ; NADPH Oxidase/*genetics ; Organ Size ; Sasa ; Thyroxine/blood ; Triiodothyronine/blood ; Ursidae/anatomy & histology/*genetics/*physiology
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  • 27
    Publication Date: 2015-01-31
    Description: The 18-kilodalton translocator protein (TSPO), proposed to be a key player in cholesterol transport into mitochondria, is highly expressed in steroidogenic tissues, metastatic cancer, and inflammatory and neurological diseases such as Alzheimer's and Parkinson's. TSPO ligands, including benzodiazepine drugs, are implicated in regulating apoptosis and are extensively used in diagnostic imaging. We report crystal structures (at 1.8, 2.4, and 2.5 angstrom resolution) of TSPO from Rhodobacter sphaeroides and a mutant that mimics the human Ala(147)--〉Thr(147) polymorphism associated with psychiatric disorders and reduced pregnenolone production. Crystals obtained in the lipidic cubic phase reveal the binding site of an endogenous porphyrin ligand and conformational effects of the mutation. The three crystal structures show the same tightly interacting dimer and provide insights into the controversial physiological role of TSPO and how the mutation affects cholesterol binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Fei -- Liu, Jian -- Zheng, Yi -- Garavito, R Michael -- Ferguson-Miller, Shelagh -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- GM094625/GM/NIGMS NIH HHS/ -- GM26916/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):555-8. doi: 10.1126/science.1260590.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. fergus20@msu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635101" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Cholesterol/metabolism ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Isoquinolines/metabolism ; Ligands ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry ; Polymorphism, Single Nucleotide ; Porphyrins/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protoporphyrins/metabolism ; Receptors, GABA/chemistry/genetics ; Rhodobacter sphaeroides/*chemistry
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 28
    Publication Date: 2015-06-06
    Description: Retroviruses depend on self-assembly of their capsid proteins (core particle) to yield infectious mature virions. Despite the essential role of the retroviral core, its high polymorphism has hindered high-resolution structural analyses. Here, we report the x-ray structure of the native capsid (CA) protein from bovine leukemia virus. CA is organized as hexamers that deviate substantially from sixfold symmetry, yet adjust to make two-dimensional pseudohexagonal arrays that mimic mature retroviral cores. Intra- and interhexameric quasi-equivalent contacts are uncovered, with flexible trimeric lateral contacts among hexamers, yet preserving very similar dimeric interfaces making the lattice. The conformation of each capsid subunit in the hexamer is therefore dictated by long-range interactions, revealing how the hexamers can also assemble into closed core particles, a relevant feature of retrovirus biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Obal, G -- Trajtenberg, F -- Carrion, F -- Tome, L -- Larrieux, N -- Zhang, X -- Pritsch, O -- Buschiazzo, A -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):95-8. doi: 10.1126/science.aaa5182. Epub 2015 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Pasteur de Montevideo, Unit of Protein Biophysics, Mataojo 2020, 11400, Montevideo, Uruguay. Departamento de Inmunobiologia, Facultad de Medicina, Universidad de la Republica, Avenida General Flores 2125, 11800, Montevideo, Uruguay. ; Institut Pasteur de Montevideo, Unit of Protein Crystallography, Mataojo 2020, 11400, Montevideo, Uruguay. ; Institut Pasteur de Montevideo, Unit of Protein Biophysics, Mataojo 2020, 11400, Montevideo, Uruguay. ; Institut Pasteur, Unite de Virologie Structurale, Departement de Virologie and CNRS Unite Mixte de Recherche 3569, 28, Rue du Docteur Roux, 75015, Paris, France. ; Institut Pasteur de Montevideo, Unit of Protein Biophysics, Mataojo 2020, 11400, Montevideo, Uruguay. Departamento de Inmunobiologia, Facultad de Medicina, Universidad de la Republica, Avenida General Flores 2125, 11800, Montevideo, Uruguay. pritsch@pasteur.edu.uy alebus@pasteur.edu.uy. ; Institut Pasteur de Montevideo, Unit of Protein Crystallography, Mataojo 2020, 11400, Montevideo, Uruguay. Institut Pasteur, Department of Structural Biology and Chemistry, 25, Rue du Dr Roux, 75015, Paris, France. pritsch@pasteur.edu.uy alebus@pasteur.edu.uy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26044299" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Capsid/*chemistry ; Capsid Proteins/*chemistry/genetics ; Cattle ; Crystallography, X-Ray ; Leukemia Virus, Bovine/*chemistry/genetics ; Molecular Sequence Data ; Mutation ; Protein Multimerization ; Protein Structure, Secondary
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  • 29
    Publication Date: 2015-08-08
    Description: Cytoplasmic aggregation of TDP-43, accompanied by its nuclear clearance, is a key common pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, a limited understanding of this RNA-binding protein (RBP) impedes the clarification of pathogenic mechanisms underlying TDP-43 proteinopathy. In contrast to RBPs that regulate splicing of conserved exons, we found that TDP-43 repressed the splicing of nonconserved cryptic exons, maintaining intron integrity. When TDP-43 was depleted from mouse embryonic stem cells, these cryptic exons were spliced into messenger RNAs, often disrupting their translation and promoting nonsense-mediated decay. Moreover, enforced repression of cryptic exons prevented cell death in TDP-43-deficient cells. Furthermore, repression of cryptic exons was impaired in ALS-FTD cases, suggesting that this splicing defect could potentially underlie TDP-43 proteinopathy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ling, Jonathan P -- Pletnikova, Olga -- Troncoso, Juan C -- Wong, Philip C -- P50AG05146/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):650-5. doi: 10.1126/science.aab0983.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. wong@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250685" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*genetics ; Animals ; Base Sequence ; Cells, Cultured ; Cysteine Endopeptidases/genetics ; DNA-Binding Proteins/genetics/*physiology ; Embryonic Stem Cells ; Exons/*genetics ; Frontotemporal Dementia/*genetics ; Gene Knockout Techniques ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Protein Isoforms/genetics ; *RNA Splicing ; RNA Stability ; RNA, Messenger/metabolism ; Sequence Analysis, DNA
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  • 30
    Publication Date: 2015-04-18
    Description: Protective CD8(+) T cell-mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8(+) T cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. Generation of LEM-deficient mice confirmed these results. Through interaction with CR6 interacting factor (CRIF1), LEM controlled the levels of oxidative phosphorylation (OXPHOS) complexes and respiration, resulting in the production of pro-proliferative mitochondrial reactive oxygen species (mROS). LEM provides a link between immune activation and the expansion of protective CD8(+) T cells driven by OXPHOS and represents a pathway for the restoration of long-term protective immunity based on metabolically modified cytotoxic CD8(+) T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okoye, Isobel -- Wang, Lihui -- Pallmer, Katharina -- Richter, Kirsten -- Ichimura, Takahuru -- Haas, Robert -- Crouse, Josh -- Choi, Onjee -- Heathcote, Dean -- Lovo, Elena -- Mauro, Claudio -- Abdi, Reza -- Oxenius, Annette -- Rutschmann, Sophie -- Ashton-Rickardt, Philip G -- A9995/Cancer Research UK/United Kingdom -- AI091930/AI/NIAID NIH HHS/ -- AI45108/AI/NIAID NIH HHS/ -- FS/12/38/29640/British Heart Foundation/United Kingdom -- G0700795/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 May 29;348(6238):995-1001. doi: 10.1126/science.aaa7516. Epub 2015 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK. ; Institute of Microbiology, Eidgenossische Technische Hochschule Zurich (ETHZ), Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland. ; Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02215, USA. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; Section of Immunobiology, Division of Inflammation and Immunology, Department of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK. Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02215, USA. p.ashton-rickardt@imperial.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883318" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology/*metabolism ; Cell Cycle Proteins/metabolism ; Cell Respiration ; Immunity, Cellular ; *Immunologic Memory ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Molecular Sequence Data ; Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism
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  • 31
    Publication Date: 2015-06-27
    Description: Cardiac progenitor cells are multipotent and give rise to cardiac endothelium, smooth muscle, and cardiomyocytes. Here, we define and characterize the cardiomyoblast intermediate that is committed to the cardiomyocyte fate, and we characterize the niche signals that regulate commitment. Cardiomyoblasts express Hopx, which functions to coordinate local Bmp signals to inhibit the Wnt pathway, thus promoting cardiomyogenesis. Hopx integrates Bmp and Wnt signaling by physically interacting with activated Smads and repressing Wnt genes. The identification of the committed cardiomyoblast that retains proliferative potential will inform cardiac regenerative therapeutics. In addition, Bmp signals characterize adult stem cell niches in other tissues where Hopx-mediated inhibition of Wnt is likely to contribute to stem cell quiescence and to explain the role of Hopx as a tumor suppressor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jain, Rajan -- Li, Deqiang -- Gupta, Mudit -- Manderfield, Lauren J -- Ifkovits, Jamie L -- Wang, Qiaohong -- Liu, Feiyan -- Liu, Ying -- Poleshko, Andrey -- Padmanabhan, Arun -- Raum, Jeffrey C -- Li, Li -- Morrisey, Edward E -- Lu, Min Min -- Won, Kyoung-Jae -- Epstein, Jonathan A -- 5-T32-GM-007170/GM/NIGMS NIH HHS/ -- K08 HL119553/HL/NHLBI NIH HHS/ -- K08 HL119553-02/HL/NHLBI NIH HHS/ -- R01 HL071546/HL/NHLBI NIH HHS/ -- U01 HL100405/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):aaa6071. doi: 10.1126/science.aaa6071.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Genetics, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Cell and Developmental Biology, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. epsteinj@upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113728" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bone Morphogenetic Proteins/genetics/*metabolism ; Cell Lineage/genetics ; Gene Expression ; *Gene Expression Regulation, Developmental ; Heart/*embryology ; Homeodomain Proteins/genetics/*metabolism ; Mice ; Mice, Mutant Strains ; Molecular Sequence Data ; Muscle, Smooth/cytology/metabolism ; Myoblasts, Cardiac/cytology/*metabolism ; Organogenesis/*genetics ; Stem Cell Niche/genetics/physiology ; Tumor Suppressor Proteins/genetics/*metabolism ; Wnt Signaling Pathway/*genetics
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  • 32
    Publication Date: 2015-01-09
    Description: The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295826/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295826/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Shuyu -- Tsun, Zhi-Yang -- Wolfson, Rachel L -- Shen, Kuang -- Wyant, Gregory A -- Plovanich, Molly E -- Yuan, Elizabeth D -- Jones, Tony D -- Chantranupong, Lynne -- Comb, William -- Wang, Tim -- Bar-Peled, Liron -- Zoncu, Roberto -- Straub, Christoph -- Kim, Choah -- Park, Jiwon -- Sabatini, Bernardo L -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- F30 CA180754/CA/NCI NIH HHS/ -- F31 AG044064/AG/NIA NIH HHS/ -- F31 CA180271/CA/NCI NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R37 AI047389/AI/NIAID NIH HHS/ -- T32 GM007287/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):188-94. doi: 10.1126/science.1257132. Epub 2015 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Harvard Medical School, 260 Longwood Avenue, Boston, MA 02115, USA. ; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. ; Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. sabatini@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25567906" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems/chemistry/genetics/*metabolism ; Arginine/deficiency/*metabolism ; HEK293 Cells ; Humans ; Lysosomes/*enzymology ; Molecular Sequence Data ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes/*metabolism ; Protein Structure, Tertiary ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism
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  • 33
    Publication Date: 2015-02-01
    Description: During virus infection, the adaptor proteins MAVS and STING transduce signals from the cytosolic nucleic acid sensors RIG-I and cGAS, respectively, to induce type I interferons (IFNs) and other antiviral molecules. Here we show that MAVS and STING harbor two conserved serine and threonine clusters that are phosphorylated by the kinases IKK and/or TBK1 in response to stimulation. Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. We further show that TRIF, an adaptor protein in Toll-like receptor signaling, activates IRF3 through a similar phosphorylation-dependent mechanism. These results reveal that phosphorylation of innate adaptor proteins is an essential and conserved mechanism that selectively recruits IRF3 to activate the type I IFN pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Siqi -- Cai, Xin -- Wu, Jiaxi -- Cong, Qian -- Chen, Xiang -- Li, Tuo -- Du, Fenghe -- Ren, Junyao -- Wu, You-Tong -- Grishin, Nick V -- Chen, Zhijian J -- AI-93967/AI/NIAID NIH HHS/ -- GM-094575/GM/NIGMS NIH HHS/ -- GM-63692/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):aaa2630. doi: 10.1126/science.aaa2630. Epub 2015 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Howard Hughes Medical Institute (HHMI), University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Howard Hughes Medical Institute (HHMI), University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. Howard Hughes Medical Institute (HHMI), University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. zhijian.chen@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25636800" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/chemistry/*metabolism ; Adaptor Proteins, Vesicular Transport/chemistry/*metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Humans ; I-kappa B Kinase/metabolism ; Interferon Regulatory Factor-3/chemistry/*metabolism ; Interferon-alpha/biosynthesis ; Interferon-beta/biosynthesis ; Membrane Proteins/chemistry/*metabolism ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Binding ; Protein Multimerization ; Protein-Serine-Threonine Kinases/metabolism ; Recombinant Proteins/metabolism ; Sendai virus/physiology ; Serine/metabolism ; Signal Transduction ; Ubiquitination ; Vesiculovirus/physiology
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  • 34
    Publication Date: 2015-12-19
    Description: Voltage-gated sodium (Nav) channels propagate action potentials in excitable cells. Accordingly, Nav channels are therapeutic targets for many cardiovascular and neurological disorders. Selective inhibitors have been challenging to design because the nine mammalian Nav channel isoforms share high sequence identity and remain recalcitrant to high-resolution structural studies. Targeting the human Nav1.7 channel involved in pain perception, we present a protein-engineering strategy that has allowed us to determine crystal structures of a novel receptor site in complex with isoform-selective antagonists. GX-936 and related inhibitors bind to the activated state of voltage-sensor domain IV (VSD4), where their anionic aryl sulfonamide warhead engages the fourth arginine gating charge on the S4 helix. By opposing VSD4 deactivation, these compounds inhibit Nav1.7 through a voltage-sensor trapping mechanism, likely by stabilizing inactivated states of the channel. Residues from the S2 and S3 helices are key determinants of isoform selectivity, and bound phospholipids implicate the membrane as a modulator of channel function and pharmacology. Our results help to elucidate the molecular basis of voltage sensing and establish structural blueprints to design selective Nav channel antagonists.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahuja, Shivani -- Mukund, Susmith -- Deng, Lunbin -- Khakh, Kuldip -- Chang, Elaine -- Ho, Hoangdung -- Shriver, Stephanie -- Young, Clint -- Lin, Sophia -- Johnson, J P Jr -- Wu, Ping -- Li, Jun -- Coons, Mary -- Tam, Christine -- Brillantes, Bobby -- Sampang, Honorio -- Mortara, Kyle -- Bowman, Krista K -- Clark, Kevin R -- Estevez, Alberto -- Xie, Zhiwei -- Verschoof, Henry -- Grimwood, Michael -- Dehnhardt, Christoph -- Andrez, Jean-Christophe -- Focken, Thilo -- Sutherlin, Daniel P -- Safina, Brian S -- Starovasnik, Melissa A -- Ortwine, Daniel F -- Franke, Yvonne -- Cohen, Charles J -- Hackos, David H -- Koth, Christopher M -- Payandeh, Jian -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):aac5464. doi: 10.1126/science.aac5464.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biology, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Discovery Chemistry, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA 94080, USA. ; Department of Chemistry, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, V5G 4W8, Canada. ; Department of Neuroscience, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com. ; Department of Structural Biology, Genentech Inc., South San Francisco, CA 94080, USA. hackos.david@gene.com koth.christopher@gene.com payandeh.jian@gene.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680203" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Membrane/chemistry ; Crystallization/methods ; Crystallography, X-Ray ; DNA Mutational Analysis ; Humans ; Models, Molecular ; Molecular Sequence Data ; NAV1.7 Voltage-Gated Sodium Channel/*chemistry/genetics ; Pain Perception/drug effects ; Protein Engineering ; Protein Isoforms/antagonists & inhibitors/chemistry ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sodium Channel Blockers/*chemistry/*pharmacology ; Sulfonamides/*chemistry/*pharmacology ; Thiadiazoles/*chemistry/*pharmacology
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  • 35
    Publication Date: 2015-06-13
    Description: The spindle checkpoint of the cell division cycle senses kinetochores that are not attached to microtubules and prevents precocious onset of anaphase, which can lead to aneuploidy. The nuclear division cycle 80 complex (Ndc80C) is a major microtubule receptor at the kinetochore. Ndc80C also mediates the kinetochore recruitment of checkpoint proteins. We found that the checkpoint protein kinase monopolar spindle 1 (Mps1) directly bound to Ndc80C through two independent interactions. Both interactions involved the microtubule-binding surfaces of Ndc80C and were directly inhibited in the presence of microtubules. Elimination of one such interaction in human cells caused checkpoint defects expected from a failure to detect unattached kinetochores. Competition between Mps1 and microtubules for Ndc80C binding thus constitutes a direct mechanism for the detection of unattached kinetochores.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ji, Zhejian -- Gao, Haishan -- Yu, Hongtao -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1260-4. doi: 10.1126/science.aaa4029.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 74390, USA. ; Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 74390, USA. hongtao.yu@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068854" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding, Competitive ; *Cell Cycle ; Cell Cycle Proteins/genetics/*metabolism ; HeLa Cells ; Humans ; Kinetochores/*metabolism ; Microtubules/*metabolism ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Protein-Tyrosine Kinases/genetics/*metabolism
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  • 36
    Publication Date: 2015-07-25
    Description: Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638224/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638224/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Jeeyun -- Torta, Federico -- Masai, Kaori -- Lucast, Louise -- Czapla, Heather -- Tanner, Lukas B -- Narayanaswamy, Pradeep -- Wenk, Markus R -- Nakatsu, Fubito -- De Camilli, Pietro -- DA018343/DA/NIDA NIH HHS/ -- DK082700/DK/NIDDK NIH HHS/ -- DK45735/DK/NIDDK NIH HHS/ -- P30 DA018343/DA/NIDA NIH HHS/ -- P30 DK045735/DK/NIDDK NIH HHS/ -- R01 DK082700/DK/NIDDK NIH HHS/ -- R37 NS036251/NS/NINDS NIH HHS/ -- R37NS036251/NS/NINDS NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jul 24;349(6246):428-32. doi: 10.1126/science.aab1370.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Howard Hughes Medical Institute, Kavli Institute for Neuroscience, and Program for Cellular Neuroscience, Neurodegeneration, and Repair, Yale School of Medicine, New Haven, CT 06520, USA. ; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore. ; Department of Cell Biology, Howard Hughes Medical Institute, Kavli Institute for Neuroscience, and Program for Cellular Neuroscience, Neurodegeneration, and Repair, Yale School of Medicine, New Haven, CT 06520, USA. pietro.decamilli@yale.edu nakatsu@med.niigata-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26206935" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Transport ; Cell Membrane/*metabolism ; Endoplasmic Reticulum/*metabolism ; Gene Knockout Techniques ; HeLa Cells ; Humans ; Molecular Sequence Data ; Phosphatidylinositol Phosphates/*metabolism ; Phosphatidylserines/*metabolism ; Protein Structure, Tertiary ; Receptors, Steroid/chemistry/genetics/*metabolism
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  • 37
    Publication Date: 2015-06-27
    Description: Bacterial adaptive immunity uses CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) proteins together with CRISPR transcripts for foreign DNA degradation. In type II CRISPR-Cas systems, activation of Cas9 endonuclease for DNA recognition upon guide RNA binding occurs by an unknown mechanism. Crystal structures of Cas9 bound to single-guide RNA reveal a conformation distinct from both the apo and DNA-bound states, in which the 10-nucleotide RNA "seed" sequence required for initial DNA interrogation is preordered in an A-form conformation. This segment of the guide RNA is essential for Cas9 to form a DNA recognition-competent structure that is poised to engage double-stranded DNA target sequences. We construe this as convergent evolution of a "seed" mechanism reminiscent of that used by Argonaute proteins during RNA interference in eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Fuguo -- Zhou, Kaihong -- Ma, Linlin -- Gressel, Saskia -- Doudna, Jennifer A -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):1477-81. doi: 10.1126/science.aab1452.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. ; Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Department of Chemistry, University of California, Berkeley, CA 94720, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Innovative Genomics Initiative, University of California, Berkeley, CA 94720, USA. doudna@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113724" target="_blank"〉PubMed〈/a〉
    Keywords: Argonaute Proteins/*chemistry ; Base Sequence ; *CRISPR-Cas Systems ; Caspase 9/*chemistry/genetics ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Crystallography, X-Ray ; DNA/chemistry ; *DNA Cleavage ; Enzyme Activation ; Evolution, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Structure, Tertiary ; RNA Interference ; RNA, Guide/*chemistry ; Streptococcus pyogenes/*enzymology
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  • 38
    Publication Date: 2015-10-17
    Description: Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27 trimethylation (H3K27me3), a hallmark of gene silencing. Here we report the crystal structures of an active PRC2 complex of 170 kilodaltons from the yeast Chaetomium thermophilum in both basal and stimulated states, which contain Ezh2, Eed, and the VEFS domain of Suz12 and are bound to a cancer-associated inhibiting H3K27M peptide and a S-adenosyl-l-homocysteine cofactor. The stimulated complex also contains an additional stimulating H3K27me3 peptide. Eed is engulfed by a belt-like structure of Ezh2, and Suz12(VEFS) contacts both of these two subunits to confer an unusual split active SET domain for catalysis. Comparison of PRC2 in the basal and stimulated states reveals a mobile Ezh2 motif that responds to stimulation to allosterically regulate the active site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiao, Lianying -- Liu, Xin -- GM114576/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):aac4383. doi: 10.1126/science.aac4383. Epub 2015 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Research, Department of Obstetrics and Gynecology and Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Research, Department of Obstetrics and Gynecology and Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. xin.liu@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472914" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Catalysis ; Catalytic Domain ; Chaetomium/genetics/*metabolism ; Crystallography, X-Ray ; Fungal Proteins/antagonists & inhibitors/*chemistry/metabolism ; *Gene Silencing ; Histones/*metabolism ; Humans ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Methylation ; Molecular Sequence Data ; Mutation ; Neoplasms/genetics ; Polycomb Repressive Complex 2/antagonists & inhibitors/*chemistry/metabolism ; Protein Structure, Tertiary ; S-Adenosylhomocysteine/chemistry/metabolism ; Transcription, Genetic
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  • 39
    Publication Date: 2015-06-27
    Description: Algal blooms produce large amounts of dimethyl sulfide (DMS), a volatile with a diverse signaling role in marine food webs that is emitted to the atmosphere, where it can affect cloud formation. The algal enzymes responsible for forming DMS from dimethylsulfoniopropionate (DMSP) remain unidentified despite their critical role in the global sulfur cycle. We identified and characterized Alma1, a DMSP lyase from the bloom-forming algae Emiliania huxleyi. Alma1 is a tetrameric, redox-sensitive enzyme of the aspartate racemase superfamily. Recombinant Alma1 exhibits biochemical features identical to the DMSP lyase in E. huxleyi, and DMS released by various E. huxleyi isolates correlates with their Alma1 levels. Sequence homology searches suggest that Alma1 represents a gene family present in major, globally distributed phytoplankton taxa and in other marine organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alcolombri, Uria -- Ben-Dor, Shifra -- Feldmesser, Ester -- Levin, Yishai -- Tawfik, Dan S -- Vardi, Assaf -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):1466-9. doi: 10.1126/science.aab1586.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel. ; Bioinformatics and Biological Computing Unit, Biological Services, Weizmann Institute of Science, Rehovot 76100, Israel. ; Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. assaf.vardi@weizmann.ac.il dan.tawfik@weizmann.ac.il. ; Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel. assaf.vardi@weizmann.ac.il dan.tawfik@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113722" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/*chemistry/classification/genetics ; Amino Acid Sequence ; Bacteria/enzymology/genetics ; Carbon-Sulfur Lyases/*chemistry/classification/genetics ; Haptophyta/*enzymology/genetics ; Molecular Sequence Data ; Phylogeny ; Phytoplankton/enzymology ; RNA, Messenger/biosynthesis ; Recombinant Proteins/chemistry ; Sulfides/*metabolism
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  • 40
    Publication Date: 2015-09-26
    Description: Mitochondria fulfill central functions in cellular energetics, metabolism, and signaling. The outer membrane translocator complex (the TOM complex) imports most mitochondrial proteins, but its architecture is unknown. Using a cross-linking approach, we mapped the active translocator down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones from the intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains three Tom40 beta-barrel channels sandwiched between a central alpha-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of alpha-helical receptors, beta-barrel channels, and chaperones generates a versatile machinery that transports about 1000 different proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shiota, Takuya -- Imai, Kenichiro -- Qiu, Jian -- Hewitt, Victoria L -- Tan, Khershing -- Shen, Hsin-Hui -- Sakiyama, Noriyuki -- Fukasawa, Yoshinori -- Hayat, Sikander -- Kamiya, Megumi -- Elofsson, Arne -- Tomii, Kentaro -- Horton, Paul -- Wiedemann, Nils -- Pfanner, Nikolaus -- Lithgow, Trevor -- Endo, Toshiya -- New York, N.Y. -- Science. 2015 Sep 25;349(6255):1544-8. doi: 10.1126/science.aac6428.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia. Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. ; Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan. ; Institut fur Biochemie und Molekularbiologie, Universitat Freiburg, 79104 Freiburg, Germany. ; Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria 3800, Australia. ; Department of Biochemistry and Biophysics and Science for Life Laboratory, Stockholm University, Box 1031, 17121 Solna, Sweden. ; Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. ; Institut fur Biochemie und Molekularbiologie, Universitat Freiburg, 79104 Freiburg, Germany. Centre for Biological Signalling Studies, Universitat Freiburg, 79104 Freiburg, Germany. ; Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26404837" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cytosol/metabolism ; Mitochondrial Membrane Transport Proteins/*chemistry/metabolism ; Molecular Chaperones ; Molecular Sequence Data ; Protein Multimerization ; Protein Structure, Secondary ; Protein Transport ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism
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  • 41
    Publication Date: 2015-02-24
    Description: Notch receptors guide mammalian cell fate decisions by engaging the proteins Jagged and Delta-like (DLL). The 2.3 angstrom resolution crystal structure of the interacting regions of the Notch1-DLL4 complex reveals a two-site, antiparallel binding orientation assisted by Notch1 O-linked glycosylation. Notch1 epidermal growth factor-like repeats 11 and 12 interact with the DLL4 Delta/Serrate/Lag-2 (DSL) domain and module at the N-terminus of Notch ligands (MNNL) domains, respectively. Threonine and serine residues on Notch1 are functionalized with O-fucose and O-glucose, which act as surrogate amino acids by making specific, and essential, contacts to residues on DLL4. The elucidation of a direct chemical role for O-glycans in Notch1 ligand engagement demonstrates how, by relying on posttranslational modifications of their ligand binding sites, Notch proteins have linked their functional capacity to developmentally regulated biosynthetic pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445638/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445638/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luca, Vincent C -- Jude, Kevin M -- Pierce, Nathan W -- Nachury, Maxence V -- Fischer, Suzanne -- Garcia, K Christopher -- 1R01-GM097015/GM/NIGMS NIH HHS/ -- R01 GM097015/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):847-53. doi: 10.1126/science.1261093.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. kcgarcia@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700513" target="_blank"〉PubMed〈/a〉
    Keywords: Alagille Syndrome/genetics ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Cell Line ; Conserved Sequence ; Crystallography, X-Ray ; Fucose/chemistry ; Glucose/chemistry ; Glycosylation ; Intracellular Signaling Peptides and Proteins/*chemistry/genetics ; Ligands ; Membrane Proteins/*chemistry/genetics/ultrastructure ; Molecular Sequence Data ; Molecular Targeted Therapy ; Polysaccharides/chemistry ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics ; Protein Binding ; Protein Structure, Tertiary ; Rats ; Receptor, Notch1/*chemistry/genetics/ultrastructure ; Serine/chemistry/genetics ; Threonine/chemistry/genetics
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  • 42
    Publication Date: 2015-06-27
    Description: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winzer, Thilo -- Kern, Marcelo -- King, Andrew J -- Larson, Tony R -- Teodor, Roxana I -- Donninger, Samantha L -- Li, Yi -- Dowle, Adam A -- Cartwright, Jared -- Bates, Rachel -- Ashford, David -- Thomas, Jerry -- Walker, Carol -- Bowser, Tim A -- Graham, Ian A -- BB/K018809/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):309-12. doi: 10.1126/science.aab1852. Epub 2015 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK. ; Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK. ; GlaxoSmithKline, 1061 Mountain Highway, Post Office Box 168, Boronia, Victoria 3155, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113639" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Benzylisoquinolines/chemistry/*metabolism ; Cytochrome P-450 Enzyme System/genetics/*metabolism ; Genetic Loci ; Isoquinolines/chemistry/*metabolism ; Molecular Sequence Data ; Morphinans/chemistry/*metabolism ; Mutation ; Oxidation-Reduction ; Papaver/*enzymology/genetics ; Plant Proteins/genetics/*metabolism ; Quaternary Ammonium Compounds/chemistry/*metabolism
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  • 43
    Publication Date: 2015-02-14
    Description: Nucleotide analog inhibitors have shown clinical success in the treatment of hepatitis C virus (HCV) infection, despite an incomplete mechanistic understanding of NS5B, the viral RNA-dependent RNA polymerase. Here we study the details of HCV RNA replication by determining crystal structures of stalled polymerase ternary complexes with enzymes, RNA templates, RNA primers, incoming nucleotides, and catalytic metal ions during both primed initiation and elongation of RNA synthesis. Our analysis revealed that highly conserved active-site residues in NS5B position the primer for in-line attack on the incoming nucleotide. A beta loop and a C-terminal membrane-anchoring linker occlude the active-site cavity in the apo state, retract in the primed initiation assembly to enforce replication of the HCV genome from the 3' terminus, and vacate the active-site cavity during elongation. We investigated the incorporation of nucleotide analog inhibitors, including the clinically active metabolite formed by sofosbuvir, to elucidate key molecular interactions in the active site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Appleby, Todd C -- Perry, Jason K -- Murakami, Eisuke -- Barauskas, Ona -- Feng, Joy -- Cho, Aesop -- Fox, David 3rd -- Wetmore, Diana R -- McGrath, Mary E -- Ray, Adrian S -- Sofia, Michael J -- Swaminathan, S -- Edwards, Thomas E -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):771-5. doi: 10.1126/science.1259210.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. todd.appleby@gilead.com tedwards@be4.com. ; Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA. ; Beryllium, 7869 NE Day Road West, Bainbridge Island, WA 98110, USA. ; Beryllium, 7869 NE Day Road West, Bainbridge Island, WA 98110, USA. todd.appleby@gilead.com tedwards@be4.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678663" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; Hepacivirus/enzymology/genetics/*physiology ; Molecular Sequence Data ; Protein Structure, Secondary ; RNA Replicase/*chemistry ; RNA, Viral/*biosynthesis ; Ribonucleotides/*chemistry ; Sofosbuvir ; Uridine Monophosphate/analogs & derivatives/chemistry ; Viral Nonstructural Proteins/*chemistry ; *Virus Replication
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  • 44
    Publication Date: 2015-07-04
    Description: The scent of roses (Rosa x hybrida) is composed of hundreds of volatile molecules. Monoterpenes represent up to 70% percent of the scent content in some cultivars, such as the Papa Meilland rose. Monoterpene biosynthesis in plants relies on plastid-localized terpene synthases. Combining transcriptomic and genetic approaches, we show that the Nudix hydrolase RhNUDX1, localized in the cytoplasm, is part of a pathway for the biosynthesis of free monoterpene alcohols that contribute to fragrance in roses. The RhNUDX1 protein shows geranyl diphosphate diphosphohydrolase activity in vitro and supports geraniol biosynthesis in planta.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Magnard, Jean-Louis -- Roccia, Aymeric -- Caissard, Jean-Claude -- Vergne, Philippe -- Sun, Pulu -- Hecquet, Romain -- Dubois, Annick -- Hibrand-Saint Oyant, Laurence -- Jullien, Frederic -- Nicole, Florence -- Raymond, Olivier -- Huguet, Stephanie -- Baltenweck, Raymonde -- Meyer, Sophie -- Claudel, Patricia -- Jeauffre, Julien -- Rohmer, Michel -- Foucher, Fabrice -- Hugueney, Philippe -- Bendahmane, Mohammed -- Baudino, Sylvie -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):81-3. doi: 10.1126/science.aab0696.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire BVpam, EA3061, Universite de Lyon/Saint-Etienne, 23 Rue du Dr Michelon, F-42000, Saint-Etienne, France. ; Laboratoire BVpam, EA3061, Universite de Lyon/Saint-Etienne, 23 Rue du Dr Michelon, F-42000, Saint-Etienne, France. Laboratoire Reproduction et Developpement des Plantes UMR Institut National de la Recherche Agronomique (INRA)-CNRS, Universite Lyon 1-ENSL, Ecole Normale Superieure de Lyon, 46 Allee d'Italie, 69364 Lyon Cedex 07, France. ; Laboratoire Reproduction et Developpement des Plantes UMR Institut National de la Recherche Agronomique (INRA)-CNRS, Universite Lyon 1-ENSL, Ecole Normale Superieure de Lyon, 46 Allee d'Italie, 69364 Lyon Cedex 07, France. ; INRA, Institut de Recherche en Horticulture et Semences (INRA, AGROCAMPUS-OUEST, Universite d'Angers), SFR 4207 QUASAV, BP 60057, 49071 Beaucouze Cedex, France. ; Genomiques Fonctionnelles d'Arabidopsis, Unite de Recherche en Genomique Vegetale, UMR INRA 1165-Universite d'Evry Val d'Essonne-ERL CNRS 8196, Evry, France. ; INRA, Universite de Strasbourg, UMR 1131 Sante de la Vigne et Qualite du Vin, 28 Rue de Herrlisheim, F-68000 Colmar, France. ; Universite de Strasbourg-CNRS, UMR 7177, Institut Le Bel, 4 Rue Blaise Pascal, 67070 Strasbourg Cedex, France. ; INRA, Universite de Strasbourg, UMR 1131 Sante de la Vigne et Qualite du Vin, 28 Rue de Herrlisheim, F-68000 Colmar, France. sylvie.baudino@univ-st-etienne.fr philippe.hugueney@colmar.inra.fr mohammed.bendahmane@ens-lyon.fr. ; Laboratoire Reproduction et Developpement des Plantes UMR Institut National de la Recherche Agronomique (INRA)-CNRS, Universite Lyon 1-ENSL, Ecole Normale Superieure de Lyon, 46 Allee d'Italie, 69364 Lyon Cedex 07, France. sylvie.baudino@univ-st-etienne.fr philippe.hugueney@colmar.inra.fr mohammed.bendahmane@ens-lyon.fr. ; Laboratoire BVpam, EA3061, Universite de Lyon/Saint-Etienne, 23 Rue du Dr Michelon, F-42000, Saint-Etienne, France. sylvie.baudino@univ-st-etienne.fr philippe.hugueney@colmar.inra.fr mohammed.bendahmane@ens-lyon.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138978" target="_blank"〉PubMed〈/a〉
    Keywords: Molecular Sequence Data ; Monoterpenes/*metabolism ; *Odors ; Plastids/*enzymology ; Pyrophosphatases/*biosynthesis/genetics ; Rosa/*enzymology/genetics ; Terpenes/*metabolism ; Transcriptome ; Volatile Organic Compounds/*metabolism
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  • 45
    Publication Date: 2015-12-19
    Description: The voltage-gated calcium channel Ca(v)1.1 is engaged in the excitation-contraction coupling of skeletal muscles. The Ca(v)1.1 complex consists of the pore-forming subunit alpha1 and auxiliary subunits alpha2delta, beta, and gamma. We report the structure of the rabbit Ca(v)1.1 complex determined by single-particle cryo-electron microscopy. The four homologous repeats of the alpha1 subunit are arranged clockwise in the extracellular view. The gamma subunit, whose structure resembles claudins, interacts with the voltage-sensing domain of repeat IV (VSD(IV)), whereas the cytosolic beta subunit is located adjacent to VSD(II) of alpha1. The alpha2 subunit interacts with the extracellular loops of repeats I to III through its VWA and Cache1 domains. The structure reveals the architecture of a prototypical eukaryotic Ca(v) channel and provides a framework for understanding the function and disease mechanisms of Ca(v) and Na(v) channels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jianping -- Yan, Zhen -- Li, Zhangqiang -- Yan, Chuangye -- Lu, Shan -- Dong, Mengqiu -- Yan, Nieng -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):aad2395. doi: 10.1126/science.aad2395.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. ; National Institute of Biological Sciences, Beijing 102206, China. ; State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China. Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. nyan@tsinghua.edu.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680202" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium Channels, L-Type/*chemistry/genetics/isolation & purification ; Cell Membrane/chemistry ; Cryoelectron Microscopy ; Molecular Sequence Data ; Muscle, Skeletal/chemistry ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/isolation & purification ; Rabbits
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  • 46
    Publication Date: 2015-12-19
    Description: Speciation, the process by which new biological species arise, involves the evolution of reproductive barriers, such as hybrid sterility or inviability between populations. However, identifying hybrid incompatibility genes remains a key obstacle in understanding the molecular basis of reproductive isolation. We devised a genomic screen, which identified a cell cycle-regulation gene as the cause of male inviability in hybrids resulting from a cross between Drosophila melanogaster and D. simulans. Ablation of the D. simulans allele of this gene is sufficient to rescue the adult viability of hybrid males. This dominantly acting cell cycle regulator causes mitotic arrest and, thereby, inviability of male hybrid larvae. Our genomic method provides a facile means to accelerate the identification of hybrid incompatibility genes in other model and nonmodel systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703311/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Phadnis, Nitin -- Baker, EmilyClare P -- Cooper, Jacob C -- Frizzell, Kimberly A -- Hsieh, Emily -- de la Cruz, Aida Flor A -- Shendure, Jay -- Kitzman, Jacob O -- Malik, Harmit S -- 5T32 HD0741/HD/NICHD NIH HHS/ -- HG006283/HG/NHGRI NIH HHS/ -- R01 GM074108/GM/NIGMS NIH HHS/ -- R01 GM115914/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1552-5. doi: 10.1126/science.aac7504.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. nitin.phadnis@utah.edu hsmalik@fhcrc.org. ; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. ; Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. ; Genome Sciences, University of Washington, Seattle, WA 98195, USA. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA. ; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. nitin.phadnis@utah.edu hsmalik@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680200" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Carrier Proteins/genetics/*physiology ; Cell Cycle/*genetics ; Chimera/genetics ; Crosses, Genetic ; Drosophila melanogaster/*genetics/growth & development ; Drosophila simulans/*genetics/growth & development ; Gene Expression Regulation, Developmental ; Genes, Essential/genetics/physiology ; Genes, Insect ; Genes, Lethal/genetics/*physiology ; *Genetic Speciation ; Male ; Molecular Sequence Data ; *Reproductive Isolation
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  • 47
    Publication Date: 2015-02-07
    Description: Mapping protein sequence space is a difficult problem that necessitates the analysis of 20(N) combinations for sequences of length N. We systematically mapped the sequence space of four key residues in the Escherichia coli protein kinase PhoQ that drive recognition of its substrate PhoP. We generated a library containing all 160,000 variants of PhoQ at these positions and used a two-step selection coupled to next-generation sequencing to identify 1659 functional variants. Our results reveal extensive degeneracy in the PhoQ-PhoP interface and epistasis, with the effect of individual substitutions often highly dependent on context. Together, epistasis and the genetic code create a pattern of connectivity of functional variants in sequence space that likely constrains PhoQ evolution. Consequently, the diversity of PhoQ orthologs is substantially lower than that of functional PhoQ variants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Podgornaia, Anna I -- Laub, Michael T -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):673-7. doi: 10.1126/science.1257360.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computational & Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. laub@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657251" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence/genetics ; *Epistasis, Genetic ; Escherichia coli Proteins/*genetics/metabolism ; *Evolution, Molecular ; Gene Library ; *Genetic Code ; Molecular Sequence Data ; Protein Interaction Domains and Motifs/genetics ; Protein Interaction Mapping ; Selection, Genetic ; Substrate Specificity/genetics
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  • 48
    Publication Date: 2015-05-23
    Description: The 5' leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. By using a (2)H-edited nuclear magnetic resonance (NMR) approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (core encapsidation signal; Psi(CES)). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions. The structure reveals how translation is attenuated, Gag binding promoted, and unspliced dimeric genomes selected, by the RNA conformer that directs packaging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492308/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492308/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keane, Sarah C -- Heng, Xiao -- Lu, Kun -- Kharytonchyk, Siarhei -- Ramakrishnan, Venkateswaran -- Carter, Gregory -- Barton, Shawn -- Hosic, Azra -- Florwick, Alyssa -- Santos, Justin -- Bolden, Nicholas C -- McCowin, Sayo -- Case, David A -- Johnson, Bruce A -- Salemi, Marco -- Telesnitsky, Alice -- Summers, Michael F -- 2T34 GM008663/GM/NIGMS NIH HHS/ -- P50 GM 103297/GM/NIGMS NIH HHS/ -- P50 GM103297/GM/NIGMS NIH HHS/ -- R01 GM042561/GM/NIGMS NIH HHS/ -- R01 GM42561/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):917-21. doi: 10.1126/science.aaa9266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA. ; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-5620, USA. ; Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA. ; One Moon Scientific, Incorporated, 839 Grant Avenue, Westfield, NJ 07090, USA, and City University of New York (CUNY) Advanced Science Research Center, 85 St. Nicholas Terrace, New York, NY 10031, USA. ; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, and Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. ; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-5620, USA. summers@hhmi.umbc.edu ateles@umich.edu. ; Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA. summers@hhmi.umbc.edu ateles@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999508" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Genome, Viral ; Guanosine/chemistry ; HIV-1/*chemistry/genetics/*physiology ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Nucleic Acid Conformation ; Peptide Chain Initiation, Translational ; RNA Splicing ; RNA, Viral/*chemistry/genetics ; *Virus Assembly ; gag Gene Products, Human Immunodeficiency Virus/chemistry
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  • 49
    Publication Date: 2015-06-27
    Description: Light-gated rhodopsin cation channels from chlorophyte algae have transformed neuroscience research through their use as membrane-depolarizing optogenetic tools for targeted photoactivation of neuron firing. Photosuppression of neuronal action potentials has been limited by the lack of equally efficient tools for membrane hyperpolarization. We describe anion channel rhodopsins (ACRs), a family of light-gated anion channels from cryptophyte algae that provide highly sensitive and efficient membrane hyperpolarization and neuronal silencing through light-gated chloride conduction. ACRs strictly conducted anions, completely excluding protons and larger cations, and hyperpolarized the membrane of cultured animal cells with much faster kinetics at less than one-thousandth of the light intensity required by the most efficient currently available optogenetic proteins. Natural ACRs provide optogenetic inhibition tools with unprecedented light sensitivity and temporal precision.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764398/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764398/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Govorunova, Elena G -- Sineshchekov, Oleg A -- Janz, Roger -- Liu, Xiaoqin -- Spudich, John L -- R01 GM027750/GM/NIGMS NIH HHS/ -- R01GM027750/GM/NIGMS NIH HHS/ -- R21MH098288/MH/NIMH NIH HHS/ -- S10RR022531/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):647-50. doi: 10.1126/science.aaa7484. Epub 2015 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, TX 77030, USA. ; Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113638" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chloride Channels/classification/genetics/*physiology ; Cryptophyta/genetics/*metabolism ; HEK293 Cells ; Humans ; Ion Channel Gating ; Light ; Membrane Potentials/physiology/*radiation effects ; Molecular Sequence Data ; Neural Inhibition ; Neurons/physiology/*radiation effects ; Optogenetics/*methods ; Photic Stimulation ; Phylogeny ; Rhodopsins, Microbial/classification/genetics/*physiology ; Transfection
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  • 50
    Publication Date: 2015-10-13
    Description: The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a 〉1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Luhan -- Guell, Marc -- Niu, Dong -- George, Haydy -- Lesha, Emal -- Grishin, Dennis -- Aach, John -- Shrock, Ellen -- Xu, Weihong -- Poci, Jurgen -- Cortazio, Rebeca -- Wilkinson, Robert A -- Fishman, Jay A -- Church, George -- P50 HG005550/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1101-4. doi: 10.1126/science.aad1191. Epub 2015 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. eGenesis Biosciences, Boston, MA 02115, USA. gchurch@genetics.med.harvard.edu luhan.yang@egenesisbio.com. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. eGenesis Biosciences, Boston, MA 02115, USA. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. ; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ; Transplant Infectious Disease and Compromised Host Program, Massachusetts General Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26456528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; CRISPR-Cas Systems ; Cell Line ; Endogenous Retroviruses/*genetics ; Epithelial Cells/virology ; Gene Dosage ; Gene Targeting/*methods ; Genes, pol ; HEK293 Cells ; Humans ; Kidney/virology ; Molecular Sequence Data ; Retroviridae Infections/*prevention & control/transmission/virology ; Swine/*virology ; Transplantation, Heterologous/*methods ; *Virus Inactivation
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  • 51
    Publication Date: 2015-08-15
    Description: Most spontaneous DNA double-strand breaks (DSBs) result from replication-fork breakage. Break-induced replication (BIR), a genome rearrangement-prone repair mechanism that requires the Pol32/POLD3 subunit of eukaryotic DNA Poldelta, was proposed to repair broken forks, but how genome destabilization is avoided was unknown. We show that broken fork repair initially uses error-prone Pol32-dependent synthesis, but that mutagenic synthesis is limited to within a few kilobases from the break by Mus81 endonuclease and a converging fork. Mus81 suppresses template switches between both homologous sequences and diverged human Alu repetitive elements, highlighting its importance for stability of highly repetitive genomes. We propose that lack of a timely converging fork or Mus81 may propel genome instability observed in cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayle, Ryan -- Campbell, Ian M -- Beck, Christine R -- Yu, Yang -- Wilson, Marenda -- Shaw, Chad A -- Bjergbaek, Lotte -- Lupski, James R -- Ira, Grzegorz -- F31 NS083159/NS/NINDS NIH HHS/ -- GM080600/GM/NIGMS NIH HHS/ -- HG006542/HG/NHGRI NIH HHS/ -- NS058529/NS/NINDS NIH HHS/ -- NS083159/NS/NINDS NIH HHS/ -- R01 GM080600/GM/NIGMS NIH HHS/ -- R01 NS058529/NS/NINDS NIH HHS/ -- U54 HG006542/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):742-7. doi: 10.1126/science.aaa8391.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. ; Department of Molecular Biology and Genetics, University of Aarhus, Aarhus 8000, Denmark. ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Department of Pediatrics, and Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Texas Children's Hospital, Houston, TX 77030, USA. ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. gira@bcm.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26273056" target="_blank"〉PubMed〈/a〉
    Keywords: Alu Elements ; Base Sequence ; *DNA Breaks, Double-Stranded ; DNA Repair/*genetics ; DNA Replication/*genetics ; DNA-Binding Proteins/genetics/*metabolism ; DNA-Directed DNA Polymerase/metabolism ; Endonucleases/genetics/*metabolism ; *Genomic Instability ; Humans ; Molecular Sequence Data ; Neoplasms/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics/*metabolism
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  • 52
    Publication Date: 2015-06-06
    Description: The detailed molecular interactions between native HIV-1 capsid protein (CA) hexamers that shield the viral genome and proteins have been elusive. We report crystal structures describing interactions between CA monomers related by sixfold symmetry within hexamers (intrahexamer) and threefold and twofold symmetry between neighboring hexamers (interhexamer). The structures describe how CA builds hexagonal lattices, the foundation of mature capsids. Lattice structure depends on an adaptable hydration layer modulating interactions among CA molecules. Disruption of this layer alters interhexamer interfaces, highlighting an inherent structural variability. A CA-targeting antiviral affects capsid stability by binding across CA molecules and subtly altering interhexamer interfaces remote to the ligand-binding site. Inherent structural plasticity, hydration layer rearrangement, and effector binding affect capsid stability and have functional implications for the retroviral life cycle.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584149/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gres, Anna T -- Kirby, Karen A -- KewalRamani, Vineet N -- Tanner, John J -- Pornillos, Owen -- Sarafianos, Stefan G -- AI076119/AI/NIAID NIH HHS/ -- AI099284/AI/NIAID NIH HHS/ -- AI100890/AI/NIAID NIH HHS/ -- AI112417/AI/NIAID NIH HHS/ -- AI120860/AI/NIAID NIH HHS/ -- GM066087/GM/NIGMS NIH HHS/ -- GM103368/GM/NIGMS NIH HHS/ -- P50 GM103368/GM/NIGMS NIH HHS/ -- R01 AI076119/AI/NIAID NIH HHS/ -- R01 AI099284/AI/NIAID NIH HHS/ -- R01 AI100890/AI/NIAID NIH HHS/ -- R01 AI120860/AI/NIAID NIH HHS/ -- R01 GM066087/GM/NIGMS NIH HHS/ -- R21 AI112417/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):99-103. doi: 10.1126/science.aaa5936. Epub 2015 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Department of Chemistry, University of Missouri, Columbia, MO 65211, USA. ; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65211, USA. ; Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. ; Department of Chemistry, University of Missouri, Columbia, MO 65211, USA. Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA. ; Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. ; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65211, USA. Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA. sarafianoss@missouri.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26044298" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Capsid/*chemistry ; Crystallography, X-Ray ; HIV-1/*chemistry/genetics ; Molecular Sequence Data ; Protein Multimerization ; Protein Structure, Secondary ; gag Gene Products, Human Immunodeficiency Virus/*chemistry/genetics
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  • 53
    Publication Date: 2015-04-25
    Description: In cells, biosynthetic machinery coordinates protein synthesis and folding to optimize efficiency and minimize off-pathway outcomes. However, it has been difficult to delineate experimentally the mechanisms responsible. Using fluorescence resonance energy transfer, we studied cotranslational folding of the first nucleotide-binding domain from the cystic fibrosis transmembrane conductance regulator. During synthesis, folding occurred discretely via sequential compaction of N-terminal, alpha-helical, and alpha/beta-core subdomains. Moreover, the timing of these events was critical; premature alpha-subdomain folding prevented subsequent core formation. This process was facilitated by modulating intrinsic folding propensity in three distinct ways: delaying alpha-subdomain compaction, facilitating beta-strand intercalation, and optimizing translation kinetics via codon usage. Thus, de novo folding is translationally tuned by an integrated cellular response that shapes the cotranslational folding landscape at critical stages of synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Soo Jung -- Yoon, Jae Seok -- Shishido, Hideki -- Yang, Zhongying -- Rooney, LeeAnn A -- Barral, Jose M -- Skach, William R -- P30CA069533/CA/NCI NIH HHS/ -- P30EYE010572/PHS HHS/ -- R01DK51818/DK/NIDDK NIH HHS/ -- R01GM53457/GM/NIGMS NIH HHS/ -- S10OD012246/OD/NIH HHS/ -- S10RR025571/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):444-8. doi: 10.1126/science.aaa3974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA. ; Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77550-0620, USA. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77550-0620, USA. ; Department of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA. Cystic Fibrosis Foundation Therapeutics, Bethesda, MD 20814, USA. skachw@ohsu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908822" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Codon/chemistry/*metabolism ; Cystic Fibrosis Transmembrane Conductance ; Regulator/*biosynthesis/*chemistry/genetics ; Fluorescence Resonance Energy Transfer ; Humans ; Kinetics ; Molecular Sequence Data ; *Peptide Chain Elongation, Translational ; *Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Ribosomes/chemistry/metabolism
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  • 54
    Publication Date: 2015-01-24
    Description: Chemokines and their receptors control cell migration during development, immune system responses, and in numerous diseases, including inflammation and cancer. The structural basis of receptor:chemokine recognition has been a long-standing unanswered question due to the challenges of structure determination for membrane protein complexes. Here, we report the crystal structure of the chemokine receptor CXCR4 in complex with the viral chemokine antagonist vMIP-II at 3.1 angstrom resolution. The structure revealed a 1:1 stoichiometry and a more extensive binding interface than anticipated from the paradigmatic two-site model. The structure helped rationalize a large body of mutagenesis data and together with modeling provided insights into CXCR4 interactions with its endogenous ligand CXCL12, its ability to recognize diverse ligands, and the specificity of CC and CXC receptors for their respective chemokines.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362693/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362693/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qin, Ling -- Kufareva, Irina -- Holden, Lauren G -- Wang, Chong -- Zheng, Yi -- Zhao, Chunxia -- Fenalti, Gustavo -- Wu, Huixian -- Han, Gye Won -- Cherezov, Vadim -- Abagyan, Ruben -- Stevens, Raymond C -- Handel, Tracy M -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- R01 GM071872/GM/NIGMS NIH HHS/ -- R01 GM081763/GM/NIGMS NIH HHS/ -- R21 AI101687/AI/NIAID NIH HHS/ -- U01 GM094612/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1117-22. doi: 10.1126/science.1261064. Epub 2015 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA 92093, USA. ; University of California, San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA 92093, USA. thandel@ucsd.edu stevens@usc.edu ikufareva@ucsd.edu. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Department of Chemistry, Bridge Institute. Department of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA. ; Department of Chemistry, Bridge Institute. ; Department of Chemistry, Bridge Institute. Department of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA. thandel@ucsd.edu stevens@usc.edu ikufareva@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25612609" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chemokine CXCL12/chemistry ; Chemokines/*chemistry ; Crystallography, X-Ray ; Drug Design ; Humans ; Models, Chemical ; Molecular Sequence Data ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Receptors, CXCR4/agonists/antagonists & inhibitors/*chemistry ; Structural Homology, Protein
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  • 55
    Publication Date: 2015-08-01
    Description: The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1alpha (DD1alpha), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1alpha appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1alpha-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1alpha thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoon, Kyoung Wan -- Byun, Sanguine -- Kwon, Eunjeong -- Hwang, So-Young -- Chu, Kiki -- Hiraki, Masatsugu -- Jo, Seung-Hee -- Weins, Astrid -- Hakroush, Samy -- Cebulla, Angelika -- Sykes, David B -- Greka, Anna -- Mundel, Peter -- Fisher, David E -- Mandinova, Anna -- Lee, Sam W -- CA142805/CA/NCI NIH HHS/ -- CA149477/CA/NCI NIH HHS/ -- CA80058/CA/NCI NIH HHS/ -- DK062472/DK/NIDDK NIH HHS/ -- DK091218/DK/NIDDK NIH HHS/ -- DK093378/DK/NIDDK NIH HHS/ -- DK57683/DK/NIDDK NIH HHS/ -- S10RR027673/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):1261669. doi: 10.1126/science.1261669.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. ; Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. ; Center for Regenerative Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ; Department of Medicine, Glom-NExT Center for Glomerular Kidney Disease and Novel Experimental Therapeutics, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. swlee@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228159" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis/genetics/*immunology ; Autoimmune Diseases/genetics/immunology ; Cell Line, Tumor ; Female ; Humans ; Inflammation/genetics/immunology ; Macrophages/immunology ; Male ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Phagocytosis/*immunology ; Phosphatidylserines/*metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/*metabolism
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  • 56
    Publication Date: 2015-04-25
    Description: The Protoaurignacian culture is pivotal to the debate about the timing of the arrival of modern humans in western Europe and the demise of Neandertals. However, which group is responsible for this culture remains uncertain. We investigated dental remains associated with the Protoaurignacian. The lower deciduous incisor from Riparo Bombrini is modern human, based on its morphology. The upper deciduous incisor from Grotta di Fumane contains ancient mitochondrial DNA of a modern human type. These teeth are the oldest human remains in an Aurignacian-related archaeological context, confirming that by 41,000 calendar years before the present, modern humans bearing Protoaurignacian culture spread into southern Europe. Because the last Neandertals date to 41,030 to 39,260 calendar years before the present, we suggest that the Protoaurignacian triggered the demise of Neandertals in this area.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benazzi, S -- Slon, V -- Talamo, S -- Negrino, F -- Peresani, M -- Bailey, S E -- Sawyer, S -- Panetta, D -- Vicino, G -- Starnini, E -- Mannino, M A -- Salvadori, P A -- Meyer, M -- Paabo, S -- Hublin, J-J -- New York, N.Y. -- Science. 2015 May 15;348(6236):793-6. doi: 10.1126/science.aaa2773. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. stefano.benazzi@unibo.it. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Dipartimento di Antichita, Filosofia, Storia e Geografia, Universita di Genova, Via Balbi 2, 16126 Genova, Italy. ; Sezione di Scienze Preistoriche e Antropologiche, Dipartimento di Studi Umanistici, Corso Ercole I d'Este 32, Universita di Ferrara, 44100 Ferrara, Italy. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. Center for the Study of Human Origins, Department of Anthropology, New York University, 25 Waverly Place, New York, NY 10003, USA. ; CNR Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy. ; Museo Archeologico del Finale, Chiostri di Santa Caterina, 17024 Finale Ligure Borgo, Italy. ; Scuola di Scienze Umanistiche, Dipartimento di Studi Storici, Universita di Torino, via S. Ottavio 20, 10124 Torino, Italy. Museo Preistorico Nazionale dei Balzi Rossi, Via Balzi Rossi 9, 18039 Ventimiglia, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908660" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archaeology ; Base Sequence ; DNA, Mitochondrial/analysis/genetics ; Dental Enamel/chemistry ; *Extinction, Biological ; Genome, Mitochondrial/genetics ; Humans ; Incisor/anatomy & histology/chemistry ; Molecular Sequence Data ; Neanderthals/anatomy & histology/*classification/*genetics ; *Phylogeny ; Tooth, Deciduous/anatomy & histology/chemistry
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  • 57
    Publication Date: 2015-09-01
    Description: The nuclear pore complex (NPC) constitutes the sole gateway for bidirectional nucleocytoplasmic transport. We present the reconstitution and interdisciplinary analyses of the ~425-kilodalton inner ring complex (IRC), which forms the central transport channel and diffusion barrier of the NPC, revealing its interaction network and equimolar stoichiometry. The Nsp1*Nup49*Nup57 channel nucleoporin heterotrimer (CNT) attaches to the IRC solely through the adaptor nucleoporin Nic96. The CNT*Nic96 structure reveals that Nic96 functions as an assembly sensor that recognizes the three-dimensional architecture of the CNT, thereby mediating the incorporation of a defined CNT state into the NPC. We propose that the IRC adopts a relatively rigid scaffold that recruits the CNT to primarily form the diffusion barrier of the NPC, rather than enabling channel dilation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stuwe, Tobias -- Bley, Christopher J -- Thierbach, Karsten -- Petrovic, Stefan -- Schilbach, Sandra -- Mayo, Daniel J -- Perriches, Thibaud -- Rundlet, Emily J -- Jeon, Young E -- Collins, Leslie N -- Huber, Ferdinand M -- Lin, Daniel H -- Paduch, Marcin -- Koide, Akiko -- Lu, Vincent -- Fischer, Jessica -- Hurt, Ed -- Koide, Shohei -- Kossiakoff, Anthony A -- Hoelz, Andre -- ACB-12002/PHS HHS/ -- AGM-12006/PHS HHS/ -- P30-CA014599/CA/NCI NIH HHS/ -- R01-GM090324/GM/NIGMS NIH HHS/ -- R01-GM111461/GM/NIGMS NIH HHS/ -- U01-GM094588/GM/NIGMS NIH HHS/ -- U54-GM087519/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 2;350(6256):56-64. doi: 10.1126/science.aac9176. Epub 2015 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute of Technology, Division of Chemistry and Chemical Engineering, 1200 East California Boulevard, Pasadena, CA 91125, USA. ; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. ; Biochemistry Center of Heidelberg University, 69120 Heidelberg, Germany. ; California Institute of Technology, Division of Chemistry and Chemical Engineering, 1200 East California Boulevard, Pasadena, CA 91125, USA. hoelz@caltech.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26316600" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chaetomium/metabolism/*ultrastructure ; Fungal Proteins/chemistry/*ultrastructure ; Molecular Sequence Data ; Nuclear Pore/metabolism/*ultrastructure ; Nuclear Pore Complex Proteins/chemistry/*ultrastructure ; Nuclear Proteins/chemistry/*ultrastructure ; Protein Binding ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 58
    Publication Date: 2015-09-19
    Description: A wide variety of RNAs encode small open-reading-frame (smORF/sORF) peptides, but their functions are largely unknown. Here, we show that Drosophila polished-rice (pri) sORF peptides trigger proteasome-mediated protein processing, converting the Shavenbaby (Svb) transcription repressor into a shorter activator. A genome-wide RNA interference screen identifies an E2-E3 ubiquitin-conjugating complex, UbcD6-Ubr3, which targets Svb to the proteasome in a pri-dependent manner. Upon interaction with Ubr3, Pri peptides promote the binding of Ubr3 to Svb. Ubr3 can then ubiquitinate the Svb N terminus, which is degraded by the proteasome. The C-terminal domains protect Svb from complete degradation and ensure appropriate processing. Our data show that Pri peptides control selectivity of Ubr3 binding, which suggests that the family of sORF peptides may contain an extended repertoire of protein regulators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zanet, J -- Benrabah, E -- Li, T -- Pelissier-Monier, A -- Chanut-Delalande, H -- Ronsin, B -- Bellen, H J -- Payre, F -- Plaza, S -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1356-8. doi: 10.1126/science.aac5677.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre de Biologie du Developpement, Universite de Toulouse III-Paul Sabatier, Batiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Developpement, F-31062 Toulouse, France. ; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. ; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA. Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Neurological Research Institute, Baylor College of Medicine, Houston, TX 77030, USA. ; Centre de Biologie du Developpement, Universite de Toulouse III-Paul Sabatier, Batiment 4R3, 118 route de Narbonne, F-31062 Toulouse, France. CNRS, UMR5547, Centre de Biologie du Developpement, F-31062 Toulouse, France. francois.payre@univ-tlse3.fr serge.plaza@univ-tlse3.f.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383956" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Drosophila Proteins/chemistry/genetics/*metabolism ; Drosophila melanogaster/enzymology/genetics/*metabolism ; Gene Expression Regulation ; Molecular Sequence Data ; Open Reading Frames ; Peptides/genetics/*metabolism ; Proteasome Endopeptidase Complex/*metabolism ; Protein Structure, Tertiary ; *Proteolysis ; RNA Interference ; Transcription Factors/chemistry/genetics/*metabolism ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
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  • 59
    Publication Date: 2015-01-31
    Description: Translocator proteins (TSPOs) bind steroids and porphyrins, and they are implicated in many human diseases, for which they serve as biomarkers and therapeutic targets. TSPOs have tryptophan-rich sequences that are highly conserved from bacteria to mammals. Here we report crystal structures for Bacillus cereus TSPO (BcTSPO) down to 1.7 A resolution, including a complex with the benzodiazepine-like inhibitor PK11195. We also describe BcTSPO-mediated protoporphyrin IX (PpIX) reactions, including catalytic degradation to a previously undescribed heme derivative. We used structure-inspired mutations to investigate reaction mechanisms, and we showed that TSPOs from Xenopus and man have similar PpIX-directed activities. Although TSPOs have been regarded as transporters, the catalytic activity in PpIX degradation suggests physiological importance for TSPOs in protection against oxidative stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341906/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341906/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Youzhong -- Kalathur, Ravi C -- Liu, Qun -- Kloss, Brian -- Bruni, Renato -- Ginter, Christopher -- Kloppmann, Edda -- Rost, Burkhard -- Hendrickson, Wayne A -- GM095315/GM/NIGMS NIH HHS/ -- GM107462/GM/NIGMS NIH HHS/ -- R01 GM107462/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 30;347(6221):551-5. doi: 10.1126/science.aaa1534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. ; The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. ; The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. ; The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. Department of Informatics, Bioinformatics and Computational Biology, Technische Universitat Munchen, Garching 85748, Germany. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. The New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA. New York Structural Biology Center, Synchrotron Beamlines, Brookhaven National Laboratory, Upton, NY 11973, USA. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. wayne@xtl.cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25635100" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus cereus/*chemistry ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Isoquinolines/metabolism ; Ligands ; Membrane Transport Proteins/*chemistry/*metabolism ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Subunits/chemistry ; Protoporphyrins/metabolism ; Reactive Oxygen Species/metabolism ; Tryptophan/analysis
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  • 60
    Publication Date: 2015-05-09
    Description: In the fruit fly Drosophila, head formation is driven by a single gene, bicoid, which generates head-to-tail polarity of the main embryonic axis. Bicoid deficiency results in embryos with tail-to-tail polarity and no head. However, most insects lack bicoid, and the molecular mechanism for establishing head-to-tail polarity is poorly understood. We have identified a gene that establishes head-to-tail polarity of the mosquito-like midge, Chironomus riparius. This gene, named panish, encodes a cysteine-clamp DNA binding domain and operates through a different mechanism than bicoid. This finding, combined with the observation that the phylogenetic distributions of panish and bicoid are limited to specific families of flies, reveals frequent evolutionary changes of body axis determinants and a remarkable opportunity to study gene regulatory network evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449817/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449817/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klomp, Jeff -- Athy, Derek -- Kwan, Chun Wai -- Bloch, Natasha I -- Sandmann, Thomas -- Lemke, Steffen -- Schmidt-Ott, Urs -- 1R03HD67700-01A1/HD/NICHD NIH HHS/ -- R03 HD067700/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2015 May 29;348(6238):1040-2. doi: 10.1126/science.aaa7105. Epub 2015 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA. ; Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA. uschmid@uchicago.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25953821" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Body Patterning/*genetics ; Chironomidae/*embryology/genetics ; DNA-Binding Proteins/classification/genetics/*physiology ; Embryo, Nonmammalian/*embryology ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Homeodomain Proteins/classification/genetics/*physiology ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary/genetics ; Trans-Activators/classification/genetics/*physiology
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  • 61
    Publication Date: 2015-04-18
    Description: Measles is a highly contagious human disease. We used cryo-electron microscopy and single particle-based helical image analysis to determine the structure of the helical nucleocapsid formed by the folded domain of the measles virus nucleoprotein encapsidating an RNA at a resolution of 4.3 angstroms. The resulting pseudoatomic model of the measles virus nucleocapsid offers important insights into the mechanism of the helical polymerization of nucleocapsids of negative-strand RNA viruses, in particular via the exchange subdomains of the nucleoprotein. The structure reveals the mode of the nucleoprotein-RNA interaction and explains why each nucleoprotein of measles virus binds six nucleotides, whereas the respiratory syncytial virus nucleoprotein binds seven. It provides a rational basis for further analysis of measles virus replication and transcription, and reveals potential targets for drug design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gutsche, Irina -- Desfosses, Ambroise -- Effantin, Gregory -- Ling, Wai Li -- Haupt, Melina -- Ruigrok, Rob W H -- Sachse, Carsten -- Schoehn, Guy -- New York, N.Y. -- Science. 2015 May 8;348(6235):704-7. doi: 10.1126/science.aaa5137. Epub 2015 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France. Universite Grenoble Alpes, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France. gutsche@embl.fr. ; Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69917 Heidelberg, Germany. ; CNRS, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France. Universite Grenoble Alpes, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France. ; Universite Grenoble Alpes, IBS, 38044 Grenoble, France. CNRS, IBS, 38044 Grenoble, France. CEA, IBS, 38044 Grenoble, France. ; Institut Laue-Langevin, 38000 Grenoble, France. ; CNRS, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France. Universite Grenoble Alpes, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France. Universite Grenoble Alpes, IBS, 38044 Grenoble, France. CNRS, IBS, 38044 Grenoble, France. CEA, IBS, 38044 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883315" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cryoelectron Microscopy ; Humans ; Measles/*virology ; Measles virus/chemistry/*ultrastructure ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleocapsid/chemistry/*ultrastructure ; Nucleoproteins/chemistry/ultrastructure ; Protein Structure, Secondary ; RNA, Viral/chemistry/ultrastructure ; Viral Proteins/chemistry/ultrastructure
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  • 62
    Publication Date: 2015-06-06
    Description: The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kling, Angela -- Lukat, Peer -- Almeida, Deepak V -- Bauer, Armin -- Fontaine, Evelyne -- Sordello, Sylvie -- Zaburannyi, Nestor -- Herrmann, Jennifer -- Wenzel, Silke C -- Konig, Claudia -- Ammerman, Nicole C -- Barrio, Maria Belen -- Borchers, Kai -- Bordon-Pallier, Florence -- Bronstrup, Mark -- Courtemanche, Gilles -- Gerlitz, Martin -- Geslin, Michel -- Hammann, Peter -- Heinz, Dirk W -- Hoffmann, Holger -- Klieber, Sylvie -- Kohlmann, Markus -- Kurz, Michael -- Lair, Christine -- Matter, Hans -- Nuermberger, Eric -- Tyagi, Sandeep -- Fraisse, Laurent -- Grosset, Jacques H -- Lagrange, Sophie -- Muller, Rolf -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1106-12. doi: 10.1126/science.aaa4690.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrucken, Germany. German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany. ; Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrucken, Germany. German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany. Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany. ; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban 4001, South Africa. ; Sanofi-Aventis R&D, LGCR/Chemistry, Industriepark Hochst, 65926 Frankfurt am Main, Germany. ; Sanofi-Aventis R&D, Infectious Diseases Therapeutic Strategic Unit, 31036 Toulouse, France. ; Sanofi-Aventis R&D, Strategy, Science Policy & External Innovation (S&I), 75008 Paris, France. ; Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany. Sanofi-Aventis R&D, LGCR/Chemistry, Industriepark Hochst, 65926 Frankfurt am Main, Germany. ; Sanofi-Aventis R&D, Infectious Diseases Therapeutic Strategic Unit, 65926 Frankfurt, Germany. ; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany. Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany. ; Sanofi-Aventis R&D, Disposition Safety and Animal Research, 34184 Montpellier, France. ; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. ; Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrucken, Germany. German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany. rolf.mueller@helmholtz-hzi.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26045430" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antitubercular Agents/chemistry/*pharmacology/therapeutic use ; Bacterial Proteins/*antagonists & inhibitors ; Cell Line, Tumor ; Crystallography, X-Ray ; DNA-Directed DNA Polymerase ; Disease Models, Animal ; Drug Design ; Humans ; Mice ; Microbial Sensitivity Tests ; Molecular Sequence Data ; *Molecular Targeted Therapy ; Mycobacterium smegmatis/drug effects/enzymology ; Mycobacterium tuberculosis/*drug effects/enzymology ; Peptides, Cyclic/chemistry/*pharmacology/therapeutic use ; Protein Structure, Secondary ; Streptomyces/chemistry/drug effects/metabolism ; Tuberculosis, Multidrug-Resistant/*drug therapy/microbiology
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  • 63
    Publication Date: 2015-12-19
    Description: Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS-CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sabir, Jamal S M -- Lam, Tommy T-Y -- Ahmed, Mohamed M M -- Li, Lifeng -- Shen, Yongyi -- Abo-Aba, Salah E M -- Qureshi, Muhammd I -- Abu-Zeid, Mohamed -- Zhang, Yu -- Khiyami, Mohammad A -- Alharbi, Njud S -- Hajrah, Nahid H -- Sabir, Meshaal J -- Mutwakil, Mohammed H Z -- Kabli, Saleh A -- Alsulaimany, Faten A S -- Obaid, Abdullah Y -- Zhou, Boping -- Smith, David K -- Holmes, Edward C -- Zhu, Huachen -- Guan, Yi -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):81-4. doi: 10.1126/science.aac8608. Epub 2015 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. ; State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. ; Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Department of Nucleic Acids Research, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications, Borg El-Arab, Post Office Box 21934, Alexandria, Egypt. ; Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. ; Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Microbial Genetics Department, Genetic Engineering and Biotechnology Division, National Research Center, Dokki, Giza, Egypt. ; King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia. ; Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. ; State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. ; Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. ; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia. ; State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. zhuhch@hku.hk yguan@hku.hk. ; Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. zhuhch@hku.hk yguan@hku.hk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26678874" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Camels/*virology ; Coinfection/epidemiology/veterinary/*virology ; Coronavirus Infections/epidemiology/veterinary/*virology ; Disease Reservoirs/veterinary/*virology ; Epidemiological Monitoring ; Humans ; Middle East Respiratory Syndrome Coronavirus/classification/*genetics/*physiology ; Molecular Sequence Data ; Phylogeny ; *Recombination, Genetic ; Saudi Arabia/epidemiology
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  • 64
    Publication Date: 2015-11-21
    Description: Eukaryotic cells coordinate growth with the availability of nutrients through the mechanistic target of rapamycin complex 1 (mTORC1), a master growth regulator. Leucine is of particular importance and activates mTORC1 via the Rag guanosine triphosphatases and their regulators GATOR1 and GATOR2. Sestrin2 interacts with GATOR2 and is a leucine sensor. Here we present the 2.7 angstrom crystal structure of Sestrin2 in complex with leucine. Leucine binds through a single pocket that coordinates its charged functional groups and confers specificity for the hydrophobic side chain. A loop encloses leucine and forms a lid-latch mechanism required for binding. A structure-guided mutation in Sestrin2 that decreases its affinity for leucine leads to a concomitant increase in the leucine concentration required for mTORC1 activation in cells. These results provide a structural mechanism of amino acid sensing by the mTORC1 pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698039/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698039/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saxton, Robert A -- Knockenhauer, Kevin E -- Wolfson, Rachel L -- Chantranupong, Lynne -- Pacold, Michael E -- Wang, Tim -- Schwartz, Thomas U -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- F30 CA189333/CA/NCI NIH HHS/ -- F31 CA180271/CA/NCI NIH HHS/ -- F31 CA189437/CA/NCI NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 AI047389/AI/NIAID NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R01CA103866/CA/NCI NIH HHS/ -- S10 RR029205/RR/NCRR NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32GM007287/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):53-8. doi: 10.1126/science.aad2087. Epub 2015 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, MIT, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. ; Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Department of Biology, MIT, Cambridge, MA 02139, USA. Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. sabatini@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26586190" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Leucine/*chemistry/metabolism ; Metabolic Networks and Pathways ; Molecular Sequence Data ; Multiprotein Complexes/chemistry/genetics/*metabolism ; Mutation ; Nuclear Proteins/*chemistry/metabolism ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; TOR Serine-Threonine Kinases/chemistry/genetics/*metabolism
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  • 65
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-01-20
    Description: Human and murine mononuclear phagocytes express a high-affinity receptor for immunoglobulin G that plays a central role in macrophage antibody-dependent cellular cytotoxicity and clearance of immune complexes. The receptor (FcRI) may also be involved in CD4-independent infection of human macrophages by human immunodeficiency virus. This report describes the isolation of cDNA clones encoding the human FcRI by a ligand-mediated selection technique. Expression of the cDNAs in COS cells gave rise to immunoglobulin G binding of the expected affinity and subtype specificity. RNA blot analysis revealed expression of a 1.7-kilobase transcript in macrophages and in cells of the promonocytic cell line U937 induced with interferon-gamma. The extracellular region of FcRI consists of three immunoglobulin-like domains, two of which share homology with low-affinity receptor domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, J M -- Seed, B -- New York, N.Y. -- Science. 1989 Jan 20;243(4889):378-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2911749" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blotting, Northern ; Cercopithecus aethiops ; Cloning, Molecular ; DNA/genetics ; Gene Expression Regulation ; Humans ; Molecular Sequence Data ; Molecular Weight ; Polymorphism, Genetic ; Receptors, Fc/*genetics ; Transfection
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  • 66
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-02-24
    Description: Cruciform DNA, a non-double helix form of DNA, can be generated as an intermediate in genetic recombination as well as from palindromic sequences under the effect of supercoiling. Eukaryotic cells are equipped with a DNA-binding protein that selectively recognizes cruciform DNA. Biochemical and immunological data showed that this protein is HMG1, an evolutionarily conserved, essential, and abundant component of the nucleus. The interaction with a ubiquitous protein points to a critical role for cruciform DNA conformations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianchi, M E -- Beltrame, M -- Paonessa, G -- New York, N.Y. -- Science. 1989 Feb 24;243(4894 Pt 1):1056-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Heidleberg, Federal Republic of Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2922595" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cloning, Molecular ; DNA/genetics/*metabolism ; Electrophoresis, Polyacrylamide Gel ; High Mobility Group Proteins/genetics/isolation & purification/*metabolism ; Immunoassay ; Immunoblotting ; Liver/analysis ; Molecular Sequence Data ; Molecular Weight ; *Nucleic Acid Conformation ; Peptide Fragments/genetics/isolation & purification ; Protein Biosynthesis ; Rats ; Transcription, Genetic
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  • 67
    Publication Date: 1989-12-22
    Description: Certain inflammatory stimuli render cultured human vascular endothelial cells hyperadhesive for neutrophils. This state is transient and reversible, in part because activated endothelial cells secrete a leukocyte adhesion inhibitor (LAI). LAI was identified as endothelial interleukin-8 (IL-8), the predominant species of which is an extended amino-terminal IL-8 variant. At nanomolar concentrations, purified endothelial IL-8 and recombinant human IL-8 inhibit neutrophil adhesion to cytokine-activated endothelial monolayers and protect these monolayers from neutrophil-mediated damage. These findings suggest that endothelial-derived IL-8 may function to attenuate inflammatory events at the interface between vessel wall and blood.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gimbrone, M A Jr -- Obin, M S -- Brock, A F -- Luis, E A -- Hass, P E -- Hebert, C A -- Yip, Y K -- Leung, D W -- Lowe, D G -- Kohr, W J -- P01-HL-36028/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Dec 22;246(4937):1601-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2688092" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Factors/pharmacology ; Cell Adhesion/drug effects ; Cells, Cultured ; Chemotactic Factors/*isolation & purification/pharmacology ; Culture Media/analysis ; Cytokines ; Endothelium, Vascular/cytology/drug effects/*physiology ; Humans ; Interleukin-1/*pharmacology ; Interleukin-8 ; Interleukins/*isolation & purification/pharmacology ; Molecular Sequence Data ; Neutrophils/cytology/drug effects/*physiology ; Recombinant Proteins/pharmacology
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  • 68
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-09-01
    Description: Oligonucleotide recognition offers a powerful chemical approach for the sequence-specific binding of double-helical DNA. In the pyrimidine-Hoogsteen model, a binding size of greater than 15 homopurine base pairs affords greater than 30 discrete sequence-specific hydrogen bonds to duplex DNA. Because pyrimidine oligonucleotides limit triple helix formation to homopurine tracts, it is desirable to determine whether oligonucleotides can be used to bind all four base pairs of DNA. A general solution would allow targeting of oligonucleotides (or their analogs) to any given sequence in the human genome. A study of 20 base triplets reveals that the triple helix can be extended from homopurine to mixed sequences. Guanine contained within a pyrimidine oligonucleotide specifically recognizes thymine.adenine base pairs in duplex DNA. Such specificity allows binding at mixed sites in DNA from simian virus 40 and human immunodeficiency virus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffin, L C -- Dervan, P B -- GM-35724/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Sep 1;245(4921):967-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2549639" target="_blank"〉PubMed〈/a〉
    Keywords: *Adenine ; Base Sequence ; DNA/*genetics ; DNA, Viral/genetics ; *Guanine ; HIV/genetics ; Hydrogen Bonding ; Models, Structural ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Oligodeoxyribonucleotides ; Simian virus 40/genetics ; *Thymine
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  • 69
    Publication Date: 1989-12-08
    Description: A novel bacteriophage lambda vector system was used to express in Escherichia coli a combinatorial library of Fab fragments of the mouse antibody repertoire. The system allows rapid and easy identification of monoclonal Fab fragments in a form suitable for genetic manipulation. It was possible to generate, in 2 weeks, large numbers of monoclonal Fab fragments against a transition state analog hapten. The methods described may supersede present-day hybridoma technology and facilitate the production of catalytic and other antibodies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huse, W D -- Sastry, L -- Iverson, S A -- Kang, A S -- Alting-Mees, M -- Burton, D R -- Benkovic, S J -- Lerner, R A -- New York, N.Y. -- Science. 1989 Dec 8;246(4935):1275-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2531466" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/*biosynthesis/genetics ; Antibody Specificity ; Antigen-Antibody Reactions ; Bacteriophage lambda/*genetics ; Base Sequence ; Cloning, Molecular/methods ; Escherichia coli/genetics ; Gene Amplification ; Gene Library ; *Genetic Vectors ; Hemocyanin/analogs & derivatives/immunology ; Immunoglobulin Fab Fragments/biosynthesis ; Immunoglobulin Fragments/*biosynthesis/genetics ; Mice ; Molecular Sequence Data ; Organophosphorus Compounds/immunology ; Recombinant Proteins/biosynthesis/genetics
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  • 70
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-03-03
    Description: Monoclonal antibodies have been induced that are capable of catalyzing specific hydrolysis of the Gly-Phe bond of peptide substrates at neutral pH with a metal complex cofactor. The antibodies were produced by immunizing with a Co(III) triethylenetetramine (trien)-peptide hapten. These antibodies as a group are capable of binding trien complexes of not only Co(III) but also of numerous other metals. Six peptides were examined as possible substrates with the antibodies and various metal complexes. Two of these peptides were cleaved by several of the antibodies. One antibody was studied in detail, and cleavage was observed for the substrates with the trien complexes of Zn(II), Ga(III), Fe(III), In(III), Cu(II), Ni(II), Lu(III), Mg(II), or Mn(II) as cofactors. A turnover number of 6 x 10(-4) per second was observed for these substrates. These results demonstrate the feasibility of the use of cofactor-assisted catalysis in an antibody binding site to accomplish difficult chemical transformations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iverson, B L -- Lerner, R A -- New York, N.Y. -- Science. 1989 Mar 3;243(4895):1184-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2922606" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Antibodies, Monoclonal ; Antigens/immunology ; Binding Sites, Antibody ; Catalysis ; Chemical Phenomena ; Chemistry ; Cobalt/immunology/metabolism ; Glycine/metabolism ; Haptens/immunology ; Hydrogen-Ion Concentration ; Hydrolysis ; Immunization ; Metals/metabolism ; Mice ; Molecular Sequence Data ; Molecular Structure ; Oligopeptides/*metabolism ; Phenylalanine/metabolism ; Trientine/immunology
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  • 71
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-05-19
    Description: Biochemical and electrophysiological studies suggest that odorants induce responses in olfactory sensory neurons via an adenylate cyclase cascade mediated by a G protein. An olfactory-specific guanosine triphosphate (GTP)-binding protein alpha subunit has now been characterized and evidence is presented suggesting that this G protein, termed Golf, mediates olfaction. Messenger RNA that encodes Golf alpha is expressed in olfactory neuroephithelium but not in six other tissues tested. Moreover, within the olfactory epithelium, Golf alpha appears to be expressed only by the sensory neurons. Specific antisera were used to localize Golf alpha protein to the sensory apparatus of the receptor neurons. Golf alpha shares extensive amino acid identity (88 percent) with the stimulatory G protein, Gs alpha. The expression of Golf alpha in S49 cyc- kin- cells, a line deficient in endogenous stimulatory G proteins, demonstrates its capacity to stimulate adenylate cyclase in a heterologous system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, D T -- Reed, R R -- New York, N.Y. -- Science. 1989 May 19;244(4906):790-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Biology and Genetic Johns Hopkins School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2499043" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; GTP-Binding Proteins/analysis/genetics/*physiology ; Gene Expression Regulation ; Immunoblotting ; Immunohistochemistry ; Molecular Sequence Data ; Neurons, Afferent/analysis/*physiology ; *Odors ; Olfactory Bulb/physiology ; Olfactory Mucosa/analysis/*innervation ; RNA, Messenger/analysis/genetics ; Rats ; Sequence Homology, Nucleic Acid ; *Signal Transduction ; Tissue Distribution ; Transfection
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  • 72
    Publication Date: 1989-12-08
    Description: Vascular permeability factor (VPF) is a 40-kilodalton disulfide-linked dimeric glycoprotein that is active in increasing blood vessel permeability, endothelial cell growth, and angiogenesis. These properties suggest that the expression of VPF by tumor cells could contribute to the increased neovascularization and vessel permeability that are associated with tumor vasculature. The cDNA sequence of VPF from human U937 cells was shown to code for a 189-amino acid polypeptide that is similar in structure to the B chain of platelet-derived growth factor (PDGF-B) and other PDGF-B-related proteins. The overall identity with PDGF-B is 18%. However, all eight of the cysteines in PDGF-B were found to be conserved in human VPF, an indication that the folding of the two proteins is probably similar. Clusters of basic amino acids in the COOH-terminal halves of human VPF and PDGF-B are also prevalent. Thus, VPF appears to be related to the PDGF/v-sis family of proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keck, P J -- Hauser, S D -- Krivi, G -- Sanzo, K -- Warren, T -- Feder, J -- Connolly, D T -- New York, N.Y. -- Science. 1989 Dec 8;246(4935):1309-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Culture and Biochemistry, Monsanto Company, St. Louis, MO 63167.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2479987" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Capillary Permeability/physiology ; Cell Division/physiology ; Cloning, Molecular ; Endothelium, Vascular/*cytology ; *Growth Substances ; Guinea Pigs ; Humans ; Lymphokines/*physiology ; Molecular Sequence Data ; Neovascularization, Pathologic/physiopathology ; Oncogene Proteins v-sis ; Platelet-Derived Growth Factor/physiology ; Retroviridae Proteins, Oncogenic/physiology ; Sequence Homology, Nucleic Acid ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
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  • 73
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-11-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klausner, R D -- Harford, J B -- New York, N.Y. -- Science. 1989 Nov 17;246(4932):870-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2683086" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Gene Expression Regulation ; *Models, Genetic ; Molecular Sequence Data ; Nucleic Acid Conformation ; *Protein Biosynthesis ; RNA, Messenger/genetics ; Transcription, Genetic
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  • 74
    Publication Date: 1989-01-27
    Description: During sporulation in Bacillus subtilis, expression of developmental genes spoIVCB and cotD is induced in the mother cell compartment of the sporangium at morphological stages IV and V, respectively. A 27-kilodalton RNA polymerase sigma factor called sigma K (or sigma 27) has been found that causes weak transcription of spoIVCB and strong transcription of cotD. A 14-kD protein was also discovered that changes the specificity of sigma K-containing RNA polymerase, greatly stimulating spoIVCB transcription and markedly repressing cotD transcription. Both sigma K and the 14-kD protein are products of genes known to be required for expression of specific genes in the mother cell. Thus, sigma K directs gene expression in the mother cell and it is proposed that inactivation or sequestering of the 14-kD protein switches the temporal pattern of gene expression during the transition from stages IV to V of development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kroos, L -- Kunkel, B -- Losick, R -- GM18568/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jan 27;243(4890):526-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2492118" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus subtilis/*genetics/physiology ; Cloning, Molecular ; DNA-Directed RNA Polymerases/*genetics/isolation & purification ; Electrophoresis, Polyacrylamide Gel ; Gene Expression Regulation ; Molecular Sequence Data ; Promoter Regions, Genetic ; Sigma Factor/*genetics/isolation & purification ; Spores, Bacterial/genetics ; Transcription Factors/*genetics ; Transcription, Genetic
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  • 75
    Publication Date: 1989-08-25
    Description: The messenger RNAs specifying certain proteins involved in the inflammatory response and certain oncoproteins contain a conserved UA-rich sequence in the 3' untranslated region. This sequence, which is composed of several interspersed repeats of the octanucleotide UUAUUUAU, has been shown to destabilize mRNA in some eukaryotes. However, this effect is not seen when mRNAs are transferred to Xenopus oocytes, which made it possible to separate stability from translational regulation. For interferon, granulocyte-macrophage colony-stimulating factor, and c-fos RNAs, the UA-rich sequence was observed to preclude mRNA translation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruys, V -- Marinx, O -- Shaw, G -- Deschamps, J -- Huez, G -- New York, N.Y. -- Science. 1989 Aug 25;245(4920):852-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de Biologie Moleculaire, Universite Libre de Bruxelles, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2672333" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Colony-Stimulating Factors/*genetics ; Granulocyte-Macrophage Colony-Stimulating Factor ; Growth Substances/*genetics ; Interferon Type I/*genetics ; Molecular Sequence Data ; *Protein Biosynthesis ; *Proto-Oncogenes ; RNA, Messenger/metabolism
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  • 76
    Publication Date: 1989-04-07
    Description: Protein engineering and x-ray crystallography have been used to study the role of a surface loop that is present in pancreatic phospholipases but is absent in snake venom phospholipases. Removal of residues 62 to 66 from porcine pancreatic phospholipase A2 does not change the binding constant for micelles significantly, but it improves catalytic activity up to 16 times on micellar (zwitterionic) lecithin substrates. In contrast, the decrease in activity on negatively charged substrates is greater than fourfold. A crystallographic study of the mutant enzyme shows that the region of the deletion has a well-defined structure that differs from the structure of the wild-type enzyme. No structural changes in the active site of the enzyme were detected.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuipers, O P -- Thunnissen, M M -- de Geus, P -- Dijkstra, B W -- Drenth, J -- Verheij, H M -- de Haas, G H -- New York, N.Y. -- Science. 1989 Apr 7;244(4900):82-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2704992" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Crystallography ; Enzyme Activation ; Kinetics ; Molecular Sequence Data ; Mutation ; Pancreas/enzymology ; Phospholipases/*metabolism ; Phospholipases A/genetics/*metabolism/physiology ; Phospholipases A2 ; *Protein Conformation ; Snake Venoms/analysis ; Structure-Activity Relationship ; Swine
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  • 77
    Publication Date: 1989-06-30
    Description: Complementary DNA's that encode an adenylyl cyclase were isolated from a bovine brain library. Most of the deduced amino acid sequence of 1134 residues is divisible into two alternating sets of hydrophobic and hydrophilic domains. Each of the two large hydrophobic domains appears to contain six transmembrane spans. Each of the two large hydrophilic domains contains a sequence that is homologous to a single cytoplasmic domain of several guanylyl cyclases; these sequences may represent nucleotide binding sites. An unexpected topographical resemblance between adenylyl cyclase and various plasma membrane channels and transporters was observed. This structural complexity suggests possible, unappreciated functions for this important enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krupinski, J -- Coussen, F -- Bakalyar, H A -- Tang, W J -- Feinstein, P G -- Orth, K -- Slaughter, C -- Reed, R R -- Gilman, A G -- CA16519/CA/NCI NIH HHS/ -- GM12230/GM/NIGMS NIH HHS/ -- GM34497/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Jun 30;244(4912):1558-64.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2472670" target="_blank"〉PubMed〈/a〉
    Keywords: *Adenylyl Cyclases/genetics/isolation & purification ; Amino Acid Sequence ; Animals ; Base Sequence ; Brain/enzymology ; *Carrier Proteins ; Cattle ; Cell Line ; Cloning, Molecular ; DNA/genetics ; Electrophoresis, Polyacrylamide Gel ; *Ion Channels ; Membrane Proteins ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Protein Conformation ; Transfection
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  • 78
    Publication Date: 1989-08-18
    Description: CD4 is a cell surface glycoprotein that is thought to interact with nonpolymorphic determinants of class II major histocompatibility (MHC) molecules. CD4 is also the receptor for the human immunodeficiency virus (HIV), binding with high affinity to the HIV-1 envelope glycoprotein, gp120. Homolog-scanning mutagenesis was used to identify CD4 regions that are important in class II MHC binding and to determine whether the gp120 and class II MHC binding sites of CD4 are related. Class II MHC binding was abolished by mutations in each of the first three immunoglobulin-like domains of CD4. The gp120 binding could be abolished without affecting class II MHC binding and vice versa, although at least one mutation examined reduced both functions significantly. These findings indicate that, while there may be overlap between the gp120 and class II MHC binding sites of CD4, these sites are distinct and can be separated. Thus it should be possible to design CD4 analogs that can block HIV infectivity but intrinsically lack the ability to affect the normal immune response by binding to class II MHC molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lamarre, D -- Ashkenazi, A -- Fleury, S -- Smith, D H -- Sekaly, R P -- Capon, D J -- New York, N.Y. -- Science. 1989 Aug 18;245(4919):743-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montreal, Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2549633" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, Surface ; Binding Sites ; DNA, Recombinant ; HIV/*metabolism ; HIV Envelope Protein gp120 ; HLA-DP Antigens/immunology ; Histocompatibility Antigens Class II/*immunology ; Humans ; Hybridomas ; Mice ; Molecular Sequence Data ; Mutation ; Receptors, HIV ; Receptors, Virus/genetics/immunology/*metabolism ; Retroviridae Proteins/immunology/*metabolism ; Rosette Formation ; Structure-Activity Relationship ; T-Lymphocytes/immunology/metabolism ; Transfection
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  • 79
    Publication Date: 1989-02-24
    Description: Branched RNA-linked multicopy single-stranded DNA (msDNA) originally detected in myxobacteria has now been found in a clinical isolate of Escherichia coli. Although lacking homology in the primary structure, the E. coli msDNA is similar in secondary structure to the myxobacterial msDNA's, including the 2',5'-phosphodiester linkage between RNA and DNA. A chromosomal DNA fragment responsible for the production of msDNA was cloned in an E. coli K12 strain; its DNA sequence revealed an open reading frame (ORF) of 586 amino acid residues. The ORF shows sequence similarity with retroviral reverse transcriptases and ribonuclease H. Disruption of the ORF blocked msDNA production, indicating that this gene is essential for msDNA synthesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lampson, B C -- Sun, J -- Hsu, M Y -- Vallejo-Ramirez, J -- Inouye, S -- Inouye, M -- F32 GM11970-01A1/GM/NIGMS NIH HHS/ -- GM26843/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 24;243(4894 Pt 1):1033-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2466332" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; DNA Probes ; DNA Restriction Enzymes ; DNA, Bacterial/genetics ; DNA, Single-Stranded/analysis/biosynthesis/*genetics ; Endoribonucleases/genetics ; Escherichia coli/enzymology/*genetics ; Genes, Bacterial ; HIV/enzymology/genetics ; Human T-lymphotropic virus 1/enzymology/genetics ; Molecular Sequence Data ; Myxococcales/genetics ; Nucleic Acid Hybridization ; RNA, Bacterial/analysis/biosynthesis/*genetics ; RNA-Directed DNA Polymerase/*genetics ; Retroviridae/*enzymology/genetics ; Ribonuclease H ; Sequence Homology, Nucleic Acid ; Transformation, Bacterial
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  • 80
    Publication Date: 1989-12-22
    Description: CD16 is a low-affinity immunoglobulin G (IgG) Fc receptor that is expressed on natural killer (NK) cells, granulocytes, activated macrophages, and some T lymphocytes. Two similar genes, CD16-I and CD16-II, encode membrane glycoproteins that are anchored by phosphatidylinositol (PI)-glycan and transmembrane polypeptides, respectively. The primary structural requirements for PI-linkage were examined by constructing a series of hybrid cDNA molecules. Although both cDNA's have an identical COOH-terminal hydrophobic segment, CD16-I has Ser203 whereas CD16-II has Phe203. Conversion of Phe to Ser in CD16-II permits expression of a PI-glycan-anchored glycoprotein, whereas conversion of Ser to Phe in CD16-I prevents PI-glycan linkage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lanier, L L -- Cwirla, S -- Yu, G -- Testi, R -- Phillips, J H -- New York, N.Y. -- Science. 1989 Dec 22;246(4937):1611-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Becton Dickinson Monoclonal Center, Inc., Mountain View, CA 94043.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2531919" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/*genetics ; Antigens, Differentiation/*genetics/metabolism ; Base Sequence ; Cell Line ; Cell Membrane/immunology ; Codon/genetics ; *Genes, Immunoglobulin ; Granulocytes/immunology ; Humans ; Membrane Glycoproteins/*genetics ; Molecular Sequence Data ; *Phenylalanine ; Receptors, Fc/*genetics/metabolism ; Receptors, IgG ; *Serine ; Transfection
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  • 81
    Publication Date: 1989-12-01
    Description: Human immunodeficiency virus (HIV) isolates with reduced sensitivity to zidovudine (3'-azido-3'-deoxythymidine, AZT) from individuals with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were studied to determine the genetic basis of their resistance. Most were sequential isolates obtained at the initiation of and during therapy. Comparative nucleotide sequence analysis of the reverse transcriptase (RT) coding region from five pairs of sensitive and resistant isolates identified three predicted amino acid substitutions common to all the resistant strains (Asp67----Asn, Lys70----Arg, Thr215----Phe or Tyr) plus a fourth in three isolates (Lys219----Gln). Partially resistant isolates had combinations of these four changes. An infectious molecular clone constructed with these four mutations in RT yielded highly resistant HIV after transfection of T cells. The reproducible nature of these mutations should make it possible to develop rapid assays to predict zidovudine resistance by performing polymerase chain reaction amplification of nucleic acid from peripheral blood lymphocytes, thereby circumventing current lengthy HIV isolation and sensitivity testing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larder, B A -- Kemp, S D -- New York, N.Y. -- Science. 1989 Dec 1;246(4934):1155-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Sciences Department, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2479983" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS-Related Complex/drug therapy/microbiology ; Acquired Immunodeficiency Syndrome/drug therapy/*microbiology ; Amino Acid Sequence ; Cloning, Molecular ; Drug Resistance/genetics ; Genes, Viral ; HIV-1/drug effects/*enzymology/genetics ; Humans ; Molecular Sequence Data ; *Mutation ; RNA-Directed DNA Polymerase/*genetics ; Zidovudine/pharmacology/*therapeutic use
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  • 82
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-07-21
    Description: Ribozymes are RNA molecules that catalyze biochemical reactions. Fe(II)-EDTA, a solvent-based reagent which cleaves both double- and single-stranded RNA, was used to investigate the structure of the Tetrahymena ribozyme. Regions of cleavage alternate with regions of substantial protection along the entire RNA molecule. In particular, most of the catalytic core shows greatly reduced cleavage. These data constitute experimental evidence that an RNA enzyme, like a protein enzyme, has an interior and an exterior. Determination of positions where the phosphodiester backbone of the RNA is on the inside or on the outside of the molecule provides major constraints for modeling the three-dimensional structure of the Tetrahymena ribozyme. This approach should be generally informative for structured RNA molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Latham, J A -- Cech, T R -- GM 11227-03/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jul 21;245(4915):276-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2501870" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoradiography ; Base Sequence ; Binding Sites ; Crystallography ; Edetic Acid ; Electrophoresis, Polyacrylamide Gel ; Ferrous Compounds ; Molecular Sequence Data ; Molecular Structure ; *Nucleic Acid Conformation ; *RNA Splicing ; RNA, Catalytic ; RNA, Fungal/analysis ; *RNA, Ribosomal/analysis/metabolism ; RNA, Transfer, Phe/analysis ; Tetrahymena/*genetics
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  • 83
    Publication Date: 1989-05-26
    Description: Spondyloepiphyseal dysplasias (SED) are a heterogeneous group of inherited disorders characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems. Evidence has suggested that SED may result from structural defects in type II collagen. To confirm the validity of this hypothesis, the structure of the "candidate" type II collagen gene (COL2A1) has been directly examined in a relatively large SED family. Coarse scanning of the gene by Southern blot hybridization identified an abnormal restriction pattern in one of the affected members of the kindred. Analysis of selected genomic fragments, amplified by the polymerase chain reaction, precisely localized the molecular defect and demonstrated that all affected family members carried the same heterozygous single-exon deletion. As a consequence of the mutation, nearly 90 percent of the assembled type II collagen homotrimers are expected to contain one or more procollagen subunits harboring an interstitial deletion of 36 amino acids in the triple helical domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, B -- Vissing, H -- Ramirez, F -- Rogers, D -- Rimoin, D -- AR-38648/AR/NIAMS NIH HHS/ -- HD-22657/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1989 May 26;244(4907):978-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, State University of New York Health Science Center, Brooklyn 11203.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2543071" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Child, Preschool ; Chromosome Deletion ; Collagen/*genetics ; DNA Restriction Enzymes ; DNA-Directed DNA Polymerase ; Exons ; Female ; Gene Amplification ; Humans ; Macromolecular Substances ; Male ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Osteochondrodysplasias/*genetics ; Pedigree ; Procollagen/genetics
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  • 84
    Publication Date: 1989-04-28
    Description: Confirmed infection with HTLV-II (human T cell leukemia virus type II) has been described only in rare cases. The major limitation to serological diagnosis of HTLV-II has been the difficulty of distinguishing HTLV-II from HTLV-I (human T cell leukemia virus type I) infection, because of substantial cross-reactivity between the viruses. A sensitive modification of the polymerase chain reaction method was used to provide unambiguous molecular evidence that a significant proportion of intravenous drug abusers are infected with HTLV, and the majority of these individuals are infected with HTLV-II rather than HTLV-I. Of 23 individuals confirmed by polymerase chain reaction analysis to be infected with HTLV, 21 were identified to be infected with HTLV-II, and 2 were infected with HTLV-I. Molecular identification of an HTLV-II--infected population provides an opportunity to investigate the pathogenicity of HTLV-II in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, H -- Swanson, P -- Shorty, V S -- Zack, J A -- Rosenblatt, J D -- Chen, I S -- New York, N.Y. -- Science. 1989 Apr 28;244(4903):471-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diagnostics Division, Abbott Laboratories, North Chicago, IL 60064.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2655084" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA, Viral/analysis ; DNA-Directed DNA Polymerase ; Genes, Viral ; HTLV-I Antibodies/analysis ; HTLV-I Infections/diagnosis/epidemiology/etiology ; HTLV-II Antibodies/*analysis ; HTLV-II Infections/diagnosis/*epidemiology/etiology ; Human T-lymphotropic virus 1/genetics/immunology ; Human T-lymphotropic virus 2/genetics/immunology ; Humans ; Immunoblotting ; Immunoenzyme Techniques ; Louisiana ; Molecular Sequence Data ; Sequence Homology, Nucleic Acid ; Substance-Related Disorders/*complications
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  • 85
    Publication Date: 1989-07-07
    Description: Basic fibroblast growth factor (bFGF) participates in many processes including early developmental events, angiogenesis, wound healing, and maintenance of neuronal cell viability. A 130-kilodalton protein was isolated on the basis of its ability to specifically bind to bFGF. A complementary DNA clone was isolated with an oligonucleotide probe corresponding to determined amino acid sequences of tryptic peptide fragments of the purified protein. The putative bFGF receptor encoded by this complementary DNA is a transmembrane protein that contains three extracellular immunoglobulin-like domains, an unusual acidic region, and an intracellular tyrosine kinase domain. These domains are arranged in a pattern that is different from that of any growth factor receptor described.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, P L -- Johnson, D E -- Cousens, L S -- Fried, V A -- Williams, L T -- CA 21765/CA/NCI NIH HHS/ -- R01 HL32898/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Jul 7;245(4913):57-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2544996" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cells, Cultured ; Chick Embryo ; *Cloning, Molecular ; DNA/*genetics ; Fibroblast Growth Factors/*genetics ; Kinetics ; Mice ; Molecular Sequence Data ; Peptide Fragments/analysis ; Receptors, Cell Surface/*genetics/metabolism ; Receptors, Fibroblast Growth Factor ; Recombinant Proteins/metabolism
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  • 86
    Publication Date: 1989-08-11
    Description: The three-dimensional solution structure of a zinc finger nucleic acid binding motif has been determined by nuclear magnetic resonance (NMR) spectroscopy. Spectra of a synthetic peptide corresponding to a single zinc finger from the Xenopus protein Xfin yielded distance and dihedral angle constraints that were used to generate structures from distance geometry and restrained molecular dynamics calculations. The zinc finger is an independently folded domain with a compact globular structure in which the zinc atom is bound by two cysteine and two histidine ligands. The polypeptide backbone fold consists of a well-defined helix, starting as alpha and ending as 3(10) helix, packed against two beta strands that are arranged in a hairpin structure. A high density of basic and polar amino acid side chains on the exposed face of the helix are probably involved in DNA binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, M S -- Gippert, G P -- Soman, K V -- Case, D A -- Wright, P E -- GM 36643/GM/NIGMS NIH HHS/ -- GM38794/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Aug 11;245(4918):635-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2503871" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cysteine/metabolism ; DNA/*metabolism ; DNA-Binding Proteins/*metabolism ; Histidine/metabolism ; Hydrogen Bonding ; Magnetic Resonance Spectroscopy ; Metalloproteins/*metabolism ; Molecular Sequence Data ; Molecular Structure ; Protein Conformation ; Solutions ; Thermodynamics ; Xenopus ; Zinc/metabolism
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  • 87
    Publication Date: 1989-12-08
    Description: Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leung, D W -- Cachianes, G -- Kuang, W J -- Goeddel, D V -- Ferrara, N -- New York, N.Y. -- Science. 1989 Dec 8;246(4935):1306-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Genetech, South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2479986" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Northern ; Cattle ; Cell Division ; Cloning, Molecular ; Endothelium, Vascular/*cytology ; Gene Library ; Humans ; Lymphokines/genetics/*physiology/secretion ; Molecular Sequence Data ; Neovascularization, Pathologic/*physiopathology ; Sequence Homology, Nucleic Acid ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
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  • 88
    Publication Date: 1989-05-05
    Description: An approach based on the polymerase chain reaction has been devised to clone new members of the family of genes encoding guanosine triphosphate-binding protein (G protein)-coupled receptors. Degenerate primers corresponding to consensus sequences of the third and sixth transmembrane segments of available receptors were used to selectively amplify and clone members of this gene family from thyroid complementary DNA. Clones encoding three known receptors and four new putative receptors were obtained. Sequence comparisons established that the new genes belong to the G protein-coupled receptor family. Close structural similarity was observed between one of the putative receptors and the 5HT1a receptor. Two other molecules displayed common sequence characteristics, suggesting that they are members of a new subfamily of receptors with a very short nonglycosylated (extracellular) amino-terminal extension.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Libert, F -- Parmentier, M -- Lefort, A -- Dinsart, C -- Van Sande, J -- Maenhaut, C -- Simons, M J -- Dumont, J E -- Vassart, G -- New York, N.Y. -- Science. 1989 May 5;244(4904):569-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Recherche Interdisciplinaire, Faculte de Medecine, Universite Libre de Bruxelles, Campus Erasme, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2541503" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; *Cloning, Molecular ; DNA/genetics ; DNA-Directed DNA Polymerase ; GTP-Binding Proteins/*metabolism ; *Gene Amplification ; Humans ; Molecular Sequence Data ; Receptors, Adrenergic, alpha/genetics ; Receptors, Adrenergic, beta/genetics ; Receptors, Muscarinic/genetics ; Receptors, Neurokinin-2 ; Receptors, Neurotransmitter/*genetics ; Receptors, Serotonin/genetics ; Sequence Homology, Nucleic Acid ; Thyroid Gland/analysis ; Transcription, Genetic
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  • 89
    Publication Date: 1989-11-24
    Description: Ciliary neurotrophic factor (CNTF) is one of a small number of proteins with neurotrophic activities distinct from nerve growth factor (NGF). CNTF has now been purified and cloned and the primary structure of CNTF from rabbit sciatic nerve has been determined. Biologically active CNTF has been transiently expressed from a rabbit complementary DNA clone. CNTF is a neural effector without significant sequence homologies to any previously reported protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, L F -- Mismer, D -- Lile, J D -- Armes, L G -- Butler, E T 3rd -- Vannice, J L -- Collins, F -- New York, N.Y. -- Science. 1989 Nov 24;246(4933):1023-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Protein Chemistry Group, Synergen, Inc., Boulder, CO 80301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2587985" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Ciliary Neurotrophic Factor ; Cloning, Molecular ; DNA/genetics ; Molecular Sequence Data ; Nerve Growth Factors/*genetics ; Nerve Tissue Proteins/biosynthesis/*genetics/isolation & purification ; Rabbits ; Recombinant Proteins/biosynthesis ; Sciatic Nerve/metabolism ; Transfection
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  • 90
    Publication Date: 1989-01-13
    Description: In the polymerase chain reaction (PCR), two specific oligonucleotide primers are used to amplify the sequences between them. However, this technique is not suitable for amplifying genes that encode molecules where the 5' portion of the sequences of interest is not known, such as the T cell receptor (TCR) or immunoglobulins. Because of this limitation, a novel technique, anchored polymerase chain reaction (A-PCR), was devised that requires sequence specificity only on the 3' end of the target fragment. It was used to analyze TCR delta chain mRNA's from human peripheral blood gamma delta T cells. Most of these cells had a V delta gene segment not previously described (V delta 3), and the delta chain junctional sequences formed a discrete subpopulation compared with those previously reported.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loh, E Y -- Elliott, J F -- Cwirla, S -- Lanier, L L -- Davis, M M -- New York, N.Y. -- Science. 1989 Jan 13;243(4888):217-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Medicine and Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5402.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2463672" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Line ; Gene Amplification ; *Genes ; Humans ; Macromolecular Substances ; Molecular Sequence Data ; Oligonucleotide Probes ; RNA, Messenger/genetics ; RNA-Directed DNA Polymerase ; Receptors, Antigen, T-Cell/*genetics ; T-Lymphocytes/immunology
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  • 91
    Publication Date: 1989-07-28
    Description: A 47-kilodalton neutrophil cytosol factor (NCF-47k), required for activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase superoxide (O2-.) production, is absent in most patients with autosomal recessive chronic granulomatous disease (AR-CGD). NCF-47k cDNAs were cloned from an expression library. The largest clone predicted a 41.9-kD protein that contained an arginine and serine-rich COOH-terminal domain with potential protein kinase C phosphorylation sites. A 33-amino acid segment of NCF-47k shared 49% identity with ras p21 guanosine triphosphatase activating protein. Recombinant NCF-47k restored O2-. -producing activity to AR-CGD neutrophil cytosol in a cell-free assay. Production of active recombinant NCF-47k will enable functional regions of this molecule to be mapped.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lomax, K J -- Leto, T L -- Nunoi, H -- Gallin, J I -- Malech, H L -- New York, N.Y. -- Science. 1989 Jul 28;245(4916):409-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bacterial Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2547247" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Blotting, Northern ; Cloning, Molecular ; DNA/*genetics ; Granulomatous Disease, Chronic/enzymology/*genetics ; Humans ; Immunoblotting ; Molecular Sequence Data ; NADH, NADPH Oxidoreductases/*metabolism ; NADPH Oxidase ; Neutrophils/*metabolism ; Phosphoproteins/*genetics/metabolism ; Phosphorylation ; Recombinant Proteins/genetics/metabolism ; Superoxides/metabolism
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-11-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lomax, K J -- Leto, T L -- Nunoi, H -- Gallin, J I -- Malech, H L -- New York, N.Y. -- Science. 1989 Nov 24;246(4933):987.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2587992" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cytosol/enzymology ; DNA/genetics ; Molecular Sequence Data ; Oxidoreductases/*genetics
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  • 93
    Publication Date: 1989-01-13
    Description: An important question in protein folding is whether the natural amino and carboxyl termini and the given order of secondary structure segments are critical to the stability and to the folding pathway of proteins. Here it is shown that two circularly permuted versions of the gene of a single-domain beta alpha barrel enzyme can be expressed in Escherichia coli. The variants are enzymically active and are practically indistinguishable from the original enzyme by several structural and spectroscopic criteria, despite the creation of new termini and the cleavage of a surface loop. This novel genetic approach should be useful for protein folding studies both in vitro and in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luger, K -- Hommel, U -- Herold, M -- Hofsteenge, J -- Kirschner, K -- New York, N.Y. -- Science. 1989 Jan 13;243(4888):206-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abteilung Biophysikalische Chemie, Universitat Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2643160" target="_blank"〉PubMed〈/a〉
    Keywords: *Aldose-Ketose Isomerases ; Amino Acid Sequence ; Base Sequence ; Carbohydrate Epimerases/*genetics/metabolism ; Circular Dichroism ; *Cloning, Molecular ; Enzyme Stability ; Escherichia coli/*enzymology/genetics ; *Genes ; Genetic Variation ; Kinetics ; Molecular Sequence Data ; *Protein Conformation ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet
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  • 94
    Publication Date: 1989-08-04
    Description: Complementary DNA clones, encoding the LH-hCG (luteinizing hormone-human choriogonadotropic hormone) receptor were isolated by screening a lambda gt11 library with monoclonal antibodies. The primary structure of the protein was deduced from the DNA sequence analysis; the protein contains 696 amino acids with a putative signal peptide of 27 amino acids. Hydropathy analysis suggests the existence of seven transmembrane domains that show homology with the corresponding regions of other G protein-coupled receptors. Three other types of clones corresponding to shorter proteins were observed, in which the putative transmembrane domain was absent. These probably arose through alternative splicing. RNA blot analysis showed similar patterns in testis and ovary with a major RNA of 4700 nucleotides and several minor species. The messenger RNA was expressed in COS-7 cells, yielding a protein that bound hCG with the same affinity as the testicular receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loosfelt, H -- Misrahi, M -- Atger, M -- Salesse, R -- Vu Hai-Luu Thi, M T -- Jolivet, A -- Guiochon-Mantel, A -- Sar, S -- Jallal, B -- Garnier, J -- New York, N.Y. -- Science. 1989 Aug 4;245(4917):525-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut National de la Sante et de la Recherche Medicale Unite 135, Hopital de Bicetre, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2502844" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Membrane/*metabolism ; *Cloning, Molecular ; DNA/*genetics ; Female ; GTP-Binding Proteins/metabolism ; Male ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Ovary/analysis ; Protein Sorting Signals/genetics ; RNA, Messenger/analysis/genetics ; Receptors, LH/*genetics/metabolism ; Sequence Homology, Nucleic Acid ; Swine ; Testis/analysis ; Tissue Distribution
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  • 95
    Publication Date: 1989-08-18
    Description: Keratinocyte growth factor (KGF) is a human mitogen that is specific for epithelial cells. The complementary DNA sequence of KGF demonstrates that it is a member of the fibroblast growth factor family. The KGF transcript was present in stromal cells derived from epithelial tissues. By comparison with the expression of other epithelial cell mitogens, only KGF, among known human growth factors, has the properties of a stromal mediator of epithelial cell proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finch, P W -- Rubin, J S -- Miki, T -- Ron, D -- Aaronson, S A -- New York, N.Y. -- Science. 1989 Aug 18;245(4919):752-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2475908" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Division ; Codon ; DNA/genetics/isolation & purification ; Epithelial Cells ; Epithelium/analysis/metabolism ; Fibroblast Growth Factor 10 ; Fibroblast Growth Factor 7 ; *Fibroblast Growth Factors/genetics ; Fibroblasts/metabolism ; Gene Expression Regulation ; Growth Substances/*genetics/physiology ; Humans ; Mesoderm/metabolism ; Mice ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Oligonucleotide Probes ; RNA/analysis ; Sequence Homology, Nucleic Acid ; Skin/analysis ; Tissue Distribution ; Transcription, Genetic
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  • 96
    Publication Date: 1989-07-07
    Description: Insulin receptor complementary DNA has been cloned from an insulin-resistant individual whose receptors have impaired tyrosine protein kinase activity. One of this individual's alleles has a mutation in which valine is substituted for Gly996, the third glycine in the conserved Gly-X-Gly-X-X-Gly motif in the putative binding site fo adenosine triphosphate. Expression of the mutant receptor by transfection into Chinese hamster ovary cells confirmed that the mutation impairs tyrosine kinase activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Odawara, M -- Kadowaki, T -- Yamamoto, R -- Shibasaki, Y -- Tobe, K -- Accili, D -- Bevins, C -- Mikami, Y -- Matsuura, N -- Akanuma, Y -- New York, N.Y. -- Science. 1989 Jul 7;245(4913):66-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2544998" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Diabetes Mellitus, Type 2/*genetics ; *Genes ; Humans ; Insulin Resistance ; Molecular Sequence Data ; *Mutation ; Protein-Tyrosine Kinases/*genetics ; Receptor, Insulin/*genetics
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  • 97
    Publication Date: 1989-08-11
    Description: The products of the nuclear oncogenes fos and jun are known to form heterodimers that bind to DNA and modulate transcription. Both proteins contain a leucine zipper that is important for heterodimer formation. Peptides corresponding to these leucine zippers were synthesized. When mixed, these peptides preferentially form heterodimers over homodimers by at least 1000-fold. Both homodimers and the heterodimer are parallel alpha helices. The leucine zipper regions from Fos and Jun therefore correspond to autonomous helical dimerization sites that are likely to be short coiled coils, and these regions are sufficient to determine the specificity of interaction between Fos and Jun. The Fos leucine zipper forms a relatively unstable homodimer. Instability of homodimers provides a thermodynamic driving force for preferential heterodimer formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Shea, E K -- Rutkowski, R -- Stafford, W F 3rd -- Kim, P S -- RR05711/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1989 Aug 11;245(4918):646-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2503872" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Circular Dichroism ; *DNA-Binding Proteins ; Disulfides ; *Leucine ; Macromolecular Substances ; Molecular Sequence Data ; Peptide Fragments/chemical synthesis ; Protein Conformation ; *Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-jun ; *Transcription Factors
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  • 98
    Publication Date: 1989-03-31
    Description: The tpa-1 gene mediates the action of tumor-promoting phorbol esters in the nematode Caenorhabditis elegans. A genomic fragment that constitutes a portion of the tpa-1 gene was cloned by Tc1 transposon tagging and was used as a probe to screen a nematode complementary DNA library. One of the isolated complementary DNA clones had a nucleotide sequence that predicts a polypeptide of 526 amino acids. The predicted amino acid sequence revealed that the predicted tpa-1 protein sequence is highly similar to protein kinase C molecules from various animals, including man.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabuse, Y -- Nishiwaki, K -- Miwa, J -- New York, N.Y. -- Science. 1989 Mar 31;243(4899):1713-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fundamental Research Laboratories, NEC Corporation, Kawasaki, Kanagawa, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2538925" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Caenorhabditis/*drug effects/genetics ; Cloning, Molecular ; Codon ; DNA/genetics ; DNA Restriction Enzymes ; Drug Resistance/genetics ; Genetic Markers ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Phenotype ; Phorbol Esters/*pharmacology ; Protein Kinase C/*genetics ; Sequence Homology, Nucleic Acid
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  • 99
    Publication Date: 1989-09-01
    Description: The structure and function of transcription factors of higher plants was studied by isolating cDNA clones encoding a wheat sequence-specific DNA binding protein. A hexameric nucleotide motif, ACGTCA, is located upstream from the TATA box of several plant histone genes. It has been suggested that this motif is essential for efficient transcription of the wheat histone H3 gene. A wheat nuclear protein, HBP-1 (histone DNA binding protein-1), which specifically binds to the hexameric motif, has previously been identified as a putative transcription factor. A cDNA clone encoding HBP-1 has been isolated on the basis of specific binding of HBP-1 to the hexameric motif. The deduced amino acid sequence indicates that HBP-1 contains the leucine zipper motif, which represents a characteristic property of several eukaryotic transcription factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabata, T -- Takase, H -- Takayama, S -- Mikami, K -- Nakatsuka, A -- Kawata, T -- Nakayama, T -- Iwabuchi, M -- New York, N.Y. -- Science. 1989 Sep 1;245(4921):965-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Botany, Faculty of Science, Kyoto University, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2772648" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; DNA/genetics ; DNA-Binding Proteins/*genetics ; *Genes ; Genes, Regulator ; Histones/*genetics ; Information Systems ; *Leucine ; Methylation ; Molecular Sequence Data ; Nuclear Proteins/*genetics ; Nucleic Acid Hybridization ; Plants/*genetics ; *Transcription, Genetic ; Triticum/genetics
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  • 100
    Publication Date: 1989-10-06
    Description: For the IIIB isolate of human immunodeficiency virus type-1 (HIV-1), the immunodominant determinant of the envelope protein gp160 for cytotoxic T lymphocytes (CTLs) of H-2d mice is in a region of high sequence variability among HIV-1 isolates. The general requirements for CTL recognition of peptide antigens and the relation of recognition requirements to the natural variation in sequence of the HIV were investigated. For this purpose, a CTL line specific for the homologous segment of the envelope from the MN isolate of HIV-1 and restricted by the same class I major histocompatibility (MHC) molecule (Dd) as the IIIB-specific CTLs was raised from mice immunized with MN-env-recombinant vaccinia virus. The IIIB-specific and MN-specific CTLs were completely non-cross-reactive. Reciprocal exchange of a single amino acid between the two peptide sequences, which differed in 6 of 15 residues, led to a complete reversal of the specificity of the peptides in sensitizing targets, such that the IIIB-specific CTLs lysed targets exposed to the singly substituted MN peptide and vice versa. These data indicate the importance of single residues in defining peptide epitopic specificity and have implications for both the effect of immune pressure on selection of viral mutants and the design of effective vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, H -- Merli, S -- Putney, S D -- Houghten, R -- Moss, B -- Germain, R N -- Berzofsky, J A -- New York, N.Y. -- Science. 1989 Oct 6;246(4926):118-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metabolism Branch, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2789433" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Genes, MHC Class I ; HIV Envelope Protein gp160 ; HIV-1/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Molecular Sequence Data ; Retroviridae Proteins/*immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Envelope Proteins/*immunology
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