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  • Amino Acid Sequence  (994)
  • Signal Transduction  (332)
  • American Association for the Advancement of Science (AAAS)  (1,269)
  • American Chemical Society (ACS)
  • 2010-2014  (431)
  • 1990-1994  (838)
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  • 1
    Publication Date: 2014-04-12
    Description: Plant embryogenesis initiates with the establishment of an apical-basal axis; however, the molecular mechanisms accompanying this early event remain unclear. Here, we show that a small cysteine-rich peptide family is required for formation of the zygotic basal cell lineage and proembryo patterning in Arabidopsis. EMBRYO SURROUNDING FACTOR 1 (ESF1) peptides accumulate before fertilization in central cell gametes and thereafter in embryo-surrounding endosperm cells. Biochemical and structural analyses revealed cleavage of ESF1 propeptides to form biologically active mature peptides. Further, these peptides act in a non-cell-autonomous manner and synergistically with the receptor-like kinase SHORT SUSPENSOR to promote suspensor elongation through the YODA mitogen-activated protein kinase pathway. Our findings demonstrate that the second female gamete and its sexually derived endosperm regulate early embryonic patterning in flowering plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Costa, Liliana M -- Marshall, Eleanor -- Tesfaye, Mesfin -- Silverstein, Kevin A T -- Mori, Masashi -- Umetsu, Yoshitaka -- Otterbach, Sophie L -- Papareddy, Ranjith -- Dickinson, Hugh G -- Boutiller, Kim -- VandenBosch, Kathryn A -- Ohki, Shinya -- Gutierrez-Marcos, Jose F -- BB/F008082/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/L003023/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/L003023/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):168-72. doi: 10.1126/science.1243005.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, University of Oxford, South Parks Road, OX1 3RB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24723605" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/*embryology/genetics ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; *Body Patterning ; Endosperm/embryology/genetics ; Flowers/*embryology/genetics ; Gene Duplication ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Gene Knockout Techniques ; Interleukin-1 Receptor-Associated Kinases/metabolism ; MAP Kinase Kinase Kinases/metabolism ; Molecular Sequence Data ; Peptides/chemistry/genetics/metabolism ; Seeds/*embryology/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-05-17
    Description: A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinohara, Hisaaki -- Behar, Marcelo -- Inoue, Kentaro -- Hiroshima, Michio -- Yasuda, Tomoharu -- Nagashima, Takeshi -- Kimura, Shuhei -- Sanjo, Hideki -- Maeda, Shiori -- Yumoto, Noriko -- Ki, Sewon -- Akira, Shizuo -- Sako, Yasushi -- Hoffmann, Alexander -- Kurosaki, Tomohiro -- Okada-Hatakeyama, Mariko -- 5R01CA141722/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 May 16;344(6185):760-4. doi: 10.1126/science.1250020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ; Laboratory for Cell Signaling Dynamics, RIKEN Quantitative Biology Center (QBiC), 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan. Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Graduate School of Engineering, Tottori University 4-101, Koyama-minami, Tottori 680-8552, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ; Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; CARD Signaling Adaptor Proteins/genetics/*metabolism ; Cell Line ; Chickens ; Feedback, Physiological ; Guanylate Cyclase/genetics/*metabolism ; I-kappa B Kinase/*metabolism ; MAP Kinase Kinase Kinases/genetics/*metabolism ; Mice ; Mice, Knockout ; Mutation ; NF-kappa B/*agonists ; Phosphorylation ; Receptors, Antigen, B-Cell/genetics/*metabolism ; Serine/genetics/metabolism ; Signal Transduction
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-09-23
    Description: Ribonucleotide reductase (RNR) supplies the balanced pools of deoxynucleotide triphosphates (dNTPs) necessary for DNA replication and maintenance of genomic integrity. RNR is subject to allosteric regulatory mechanisms in all eukaryotes, as well as to control by small protein inhibitors Sml1p and Spd1p in budding and fission yeast, respectively. Here, we show that the metazoan protein IRBIT forms a deoxyadenosine triphosphate (dATP)-dependent complex with RNR, which stabilizes dATP in the activity site of RNR and thus inhibits the enzyme. Formation of the RNR-IRBIT complex is regulated through phosphorylation of IRBIT, and ablation of IRBIT expression in HeLa cells causes imbalanced dNTP pools and altered cell cycle progression. We demonstrate a mechanism for RNR regulation in higher eukaryotes that acts by enhancing allosteric RNR inhibition by dATP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arnaoutov, Alexei -- Dasso, Mary -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1512-5. doi: 10.1126/science.1251550.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. arnaouta@mail.nih.gov. ; Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 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/25237103" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Catalytic Domain ; Deoxyadenine Nucleotides/*metabolism ; HeLa Cells ; Humans ; Immunoprecipitation ; Lectins, C-Type/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Molecular Sequence Data ; Phosphorylation ; Ribonucleotide Reductases/*antagonists & inhibitors/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-02-08
    Description: Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of gamma-aminobutyric acid type A (GABA(A)) receptor (GABA(A)R)-mediated inhibition and cytoplasmic volume regulation. Equilibrative cation-chloride cotransporters (CCCs) move Cl(-) across the membrane, but accumulating evidence suggests factors other than the bulk concentrations of transported ions determine [Cl(-)](i). Measurement of [Cl(-)](i) in murine brain slice preparations expressing the transgenic fluorophore Clomeleon demonstrated that cytoplasmic impermeant anions ([A](i)) and polyanionic extracellular matrix glycoproteins ([A](o)) constrain the local [Cl(-)]. CCC inhibition had modest effects on [Cl(-)](i) and neuronal volume, but substantial changes were produced by alterations of the balance between [A](i) and [A](o). Therefore, CCCs are important elements of Cl(-) homeostasis, but local impermeant anions determine the homeostatic set point for [Cl(-)], and hence, neuronal volume and the polarity of local GABA(A)R signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220679/" 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/PMC4220679/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glykys, J -- Dzhala, V -- Egawa, K -- Balena, T -- Saponjian, Y -- Kuchibhotla, K V -- Bacskai, B J -- Kahle, K T -- Zeuthen, T -- Staley, K J -- NS 40109-06/NS/NINDS NIH HHS/ -- R01 EB000768/EB/NIBIB NIH HHS/ -- R01 NS040109/NS/NINDS NIH HHS/ -- R01 NS074772/NS/NINDS NIH HHS/ -- R25 NS065743/NS/NINDS NIH HHS/ -- S10 RR025645/RR/NCRR NIH HHS/ -- U41 RR019703/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):670-5. doi: 10.1126/science.1245423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism ; Cell Membrane Permeability ; Cell Polarity ; Chloride Channels/*metabolism ; Chlorides/*metabolism ; Cytoplasm/metabolism ; Extracellular Matrix Proteins/metabolism ; Glycoproteins/metabolism ; Mice ; Mice, Transgenic ; Neurons/*metabolism ; Receptors, GABA-A/*metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Signal Transduction
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-04-26
    Description: Using light to silence electrical activity in targeted cells is a major goal of optogenetics. Available optogenetic proteins that directly move ions to achieve silencing are inefficient, pumping only a single ion per photon across the cell membrane rather than allowing many ions per photon to flow through a channel pore. Building on high-resolution crystal-structure analysis, pore vestibule modeling, and structure-guided protein engineering, we designed and characterized a class of channelrhodopsins (originally cation-conducting) converted into chloride-conducting anion channels. These tools enable fast optical inhibition of action potentials and can be engineered to display step-function kinetics for stable inhibition, outlasting light pulses and for orders-of-magnitude-greater light sensitivity of inhibited cells. The resulting family of proteins defines an approach to more physiological, efficient, and sensitive optogenetic inhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096039/" 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/PMC4096039/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berndt, Andre -- Lee, Soo Yeun -- Ramakrishnan, Charu -- Deisseroth, Karl -- R01 DA020794/DA/NIDA NIH HHS/ -- R01 MH075957/MH/NIMH NIH HHS/ -- R01 MH086373/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):420-4. doi: 10.1126/science.1252367.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763591" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Amino Acid Sequence ; Animals ; CA1 Region, Hippocampal/cytology ; CA3 Region, Hippocampal/cytology ; Chloride Channels/*chemistry/*metabolism ; Chlorides/*metabolism ; HEK293 Cells ; Humans ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Neurons/*physiology ; Optogenetics ; Patch-Clamp Techniques ; Protein Engineering ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/chemistry/metabolism ; Rhodopsin/*chemistry/genetics/*metabolism
    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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  • 6
    Publication Date: 2014-03-08
    Description: The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein-coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991565/" 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/PMC3991565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Huixian -- Wang, Chong -- Gregory, Karen J -- Han, Gye Won -- Cho, Hyekyung P -- Xia, Yan -- Niswender, Colleen M -- Katritch, Vsevolod -- Meiler, Jens -- Cherezov, Vadim -- Conn, P Jeffrey -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK097376/DK/NIDDK NIH HHS/ -- R01 GM080403/GM/NIGMS NIH HHS/ -- R01 GM099842/GM/NIGMS NIH HHS/ -- R01 MH062646/MH/NIMH NIH HHS/ -- R01 MH090192/MH/NIMH NIH HHS/ -- R01 NS031373/NS/NINDS NIH HHS/ -- R21 NS078262/NS/NINDS NIH HHS/ -- R37 NS031373/NS/NINDS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):58-64. doi: 10.1126/science.1249489. Epub 2014 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24603153" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Allosteric Site ; Amino Acid Sequence ; Benzamides/*chemistry/*metabolism ; Binding Sites ; Cholesterol ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Metabotropic Glutamate/*chemistry/*metabolism ; Structure-Activity Relationship ; Thiazoles/*chemistry/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-03-22
    Description: The development of cells specialized for water conduction or support is a striking innovation of plants that has enabled them to colonize land. The NAC transcription factors regulate the differentiation of these cells in vascular plants. However, the path by which plants with these cells have evolved from their nonvascular ancestors is unclear. We investigated genes of the moss Physcomitrella patens that encode NAC proteins. Loss-of-function mutants formed abnormal water-conducting and supporting cells, as well as malformed sporophyte cells, and overexpression induced ectopic differentiation of water-conducting-like cells. Our results show conservation of transcriptional regulation and cellular function between moss and Arabidopsis thaliana water-conducting cells. The conserved genetic basis suggests roles for NAC proteins in the adaptation of plants to land.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Bo -- Ohtani, Misato -- Yamaguchi, Masatoshi -- Toyooka, Kiminori -- Wakazaki, Mayumi -- Sato, Mayuko -- Kubo, Minoru -- Nakano, Yoshimi -- Sano, Ryosuke -- Hiwatashi, Yuji -- Murata, Takashi -- Kurata, Tetsuya -- Yoneda, Arata -- Kato, Ko -- Hasebe, Mitsuyasu -- Demura, Taku -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1505-8. doi: 10.1126/science.1248417. Epub 2014 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24652936" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Amino Acid Sequence ; Arabidopsis/genetics/*physiology ; Bryopsida/genetics/*physiology ; *Gene Expression Regulation, Plant ; Genetic Loci ; Genome, Plant ; Molecular Sequence Data ; Plant Proteins/genetics/*physiology ; Plant Stems/growth & development ; Trans-Activators/genetics/*physiology ; Transcription, Genetic ; Water/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-08-26
    Description: Sensory systems define an animal's capacity for perception and can evolve to promote survival in new environmental niches. We have uncovered a noncanonical mechanism for sweet taste perception that evolved in hummingbirds since their divergence from insectivorous swifts, their closest relatives. We observed the widespread absence in birds of an essential subunit (T1R2) of the only known vertebrate sweet receptor, raising questions about how specialized nectar feeders such as hummingbirds sense sugars. Receptor expression studies revealed that the ancestral umami receptor (the T1R1-T1R3 heterodimer) was repurposed in hummingbirds to function as a carbohydrate receptor. Furthermore, the molecular recognition properties of T1R1-T1R3 guided taste behavior in captive and wild hummingbirds. We propose that changing taste receptor function enabled hummingbirds to perceive and use nectar, facilitating the massive radiation of hummingbird species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302410/" 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/PMC4302410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldwin, Maude W -- Toda, Yasuka -- Nakagita, Tomoya -- O'Connell, Mary J -- Klasing, Kirk C -- Misaka, Takumi -- Edwards, Scott V -- Liberles, Stephen D -- R01 DC013289/DC/NIDCD NIH HHS/ -- R01DC013289/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):929-33. doi: 10.1126/science.1255097.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, and Museum of Comparative Zoology, Cambridge, MA 02138, USA. maudebaldwin@gmail.com stephen_liberles@hms.harvard.edu. ; Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. ; Bioinformatics and Molecular Evolution Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. ; Department of Animal Science, University of California, Davis, Davis, CA 95616, USA. ; Department of Organismic and Evolutionary Biology, Harvard University, and Museum of Comparative Zoology, Cambridge, MA 02138, USA. ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. maudebaldwin@gmail.com stephen_liberles@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146290" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Mice ; Molecular Sequence Data ; Plant Nectar ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/chemistry/classification/*genetics ; Taste/*physiology ; Taste Perception/genetics/*physiology
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  • 9
    Publication Date: 2014-04-26
    Description: The hierarchical packaging of eukaryotic chromatin plays a central role in transcriptional regulation and other DNA-related biological processes. Here, we report the 11-angstrom-resolution cryogenic electron microscopy (cryo-EM) structures of 30-nanometer chromatin fibers reconstituted in the presence of linker histone H1 and with different nucleosome repeat lengths. The structures show a histone H1-dependent left-handed twist of the repeating tetranucleosomal structural units, within which the four nucleosomes zigzag back and forth with a straight linker DNA. The asymmetric binding and the location of histone H1 in chromatin play a role in the formation of the 30-nanometer fiber. Our results provide mechanistic insights into how nucleosomes compact into higher-order chromatin fibers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Feng -- Chen, Ping -- Sun, Dapeng -- Wang, Mingzhu -- Dong, Liping -- Liang, Dan -- Xu, Rui-Ming -- Zhu, Ping -- Li, Guohong -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):376-80. doi: 10.1126/science.1251413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763583" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Chromatin/chemistry/metabolism/*ultrastructure ; Cryoelectron Microscopy ; DNA/chemistry/*ultrastructure ; Histones/*chemistry/metabolism ; Imaging, Three-Dimensional ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleosomes/*ultrastructure ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; Xenopus Proteins/chemistry ; Xenopus laevis
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  • 10
    Publication Date: 2014-04-05
    Description: Development of vertebrate embryos involves tightly regulated molecular and cellular processes that progressively instruct proliferating embryonic cells about their identity and behavior. Whereas numerous gene activities have been found to be essential during early embryogenesis, little is known about the minimal conditions and factors that would be sufficient to instruct pluripotent cells to organize the embryo. Here, we show that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Peng-Fei -- Houssin, Nathalie -- Ferri-Lagneau, Karine F -- Thisse, Bernard -- Thisse, Christine -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):87-9. doi: 10.1126/science.1248252.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700857" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastula/*physiology ; Body Patterning ; Bone Morphogenetic Proteins/genetics/*physiology ; Embryo, Nonmammalian/*physiology ; *Embryonic Development ; Gastrula/physiology ; Gastrulation ; Gene Expression Regulation, Developmental ; Morphogenesis ; Nodal Protein/genetics/*physiology ; RNA, Messenger/genetics ; Signal Transduction ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*physiology
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  • 11
    Publication Date: 2014-12-06
    Description: Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280847/" 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/PMC4280847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sreeramkumar, Vinatha -- Adrover, Jose M -- Ballesteros, Ivan -- Cuartero, Maria Isabel -- Rossaint, Jan -- Bilbao, Izaskun -- Nacher, Maria -- Pitaval, Christophe -- Radovanovic, Irena -- Fukui, Yoshinori -- McEver, Rodger P -- Filippi, Marie-Dominique -- Lizasoain, Ignacio -- Ruiz-Cabello, Jesus -- Zarbock, Alexander -- Moro, Maria A -- Hidalgo, Andres -- HL03463/HL/NHLBI NIH HHS/ -- HL085607/HL/NHLBI NIH HHS/ -- HL090676/HL/NHLBI NIH HHS/ -- P01 HL085607/HL/NHLBI NIH HHS/ -- R01 HL034363/HL/NHLBI NIH HHS/ -- R01 HL090676/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1234-8. doi: 10.1126/science.1256478. Epub 2014 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. ; Unidad de Investigacion Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigacion Hospital 12 de Octubre (i+12), Madrid, Spain. ; Department of Anesthesiology and Critical Care Medicine, University of Munster and Max Planck Institute Munster, Munster, Germany. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Australia. ; Division of Immunogenetics, Department of Immunobiology and Neuroscience, Kyushu University, Japan. ; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. ; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA. ; Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany. ahidalgo@cnic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477463" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Circulation ; Blood Platelets/*immunology ; Cell Movement ; Cell Polarity ; Endothelium, Vascular/immunology ; Inflammation/blood/*immunology ; Male ; Membrane Glycoproteins ; Mice ; Mice, Inbred C57BL ; Neutrophils/*immunology ; *Platelet Activation ; Signal Transduction ; Thrombosis/*immunology ; Venules/immunology
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  • 12
    Publication Date: 2014-10-18
    Description: Nitrogen (N) is a critical nutrient for plants but is often distributed unevenly in the soil. Plants therefore have evolved a systemic mechanism by which N starvation on one side of the root system leads to a compensatory and increased nitrate uptake on the other side. Here, we study the molecular systems that support perception of N and the long-distance signaling needed to alter root development. Rootlets starved of N secrete small peptides that are translocated to the shoot and received by two leucine-rich repeat receptor kinases (LRR-RKs). Arabidopsis plants deficient in this pathway show growth retardation accompanied with N-deficiency symptoms. Thus, signaling from the root to the shoot helps the plant adapt to fluctuations in local N availability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabata, Ryo -- Sumida, Kumiko -- Yoshii, Tomoaki -- Ohyama, Kentaro -- Shinohara, Hidefumi -- Matsubayashi, Yoshikatsu -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):343-6. doi: 10.1126/science.1257800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. ; Department of Applied Molecular Biosciences, Graduate School of Bio-Agricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan. matsu@bio.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324386" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Molecular Sequence Data ; Nitrogen/*metabolism ; Peptides/*metabolism ; Plant Roots/genetics/*growth & development/metabolism ; Plant Shoots/genetics/*growth & development/metabolism ; Receptors, Peptide/genetics/*metabolism ; Signal Transduction
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  • 13
    Publication Date: 2014-07-26
    Description: Proteins that cap the ends of the actin filament are essential regulators of cytoskeleton dynamics. Whereas several proteins cap the rapidly growing barbed end, tropomodulin (Tmod) is the only protein known to cap the slowly growing pointed end. The lack of structural information severely limits our understanding of Tmod's capping mechanism. We describe crystal structures of actin complexes with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal domains of Tmod. The structures and biochemical analysis of structure-inspired mutants showed that one Tmod molecule interacts with three actin subunits at the pointed end, while also contacting two tropomyosin molecules on each side of the filament. We found that Tmod achieves high-affinity binding through several discrete low-affinity interactions, which suggests a mechanism for controlled subunit exchange at the pointed end.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367809/" 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/PMC4367809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rao, Jampani Nageswara -- Madasu, Yadaiah -- Dominguez, Roberto -- GM-0080/GM/NIGMS NIH HHS/ -- R01 GM073791/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 25;345(6195):463-7. doi: 10.1126/science.1256159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. droberto@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25061212" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*chemistry ; Actins/*chemistry ; Amino Acid Sequence ; Animals ; Crystallography, X-Ray ; Humans ; Molecular Sequence Data ; Mutation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rabbits ; Tropomodulin/*chemistry/genetics
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  • 14
    Publication Date: 2014-09-06
    Description: Pathogens traverse multiple barriers during infection, including cell membranes. We found that during this transition, pathogens carried covalently attached complement C3 into the cell, triggering immediate signaling and effector responses. Sensing of C3 in the cytosol activated mitochondrial antiviral signaling (MAVS)-dependent signaling cascades and induced proinflammatory cytokine secretion. C3 also flagged viruses for rapid proteasomal degradation, preventing their replication. This system could detect both viral and bacterial pathogens but was antagonized by enteroviruses, such as rhinovirus and poliovirus, which cleave C3 using their 3C protease. The antiviral rupintrivir inhibited 3C protease and prevented C3 cleavage, rendering enteroviruses susceptible to intracellular complement sensing. Thus, complement C3 allows cells to detect and disable pathogens that have invaded the cytosol.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172439/" 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/PMC4172439/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tam, Jerry C H -- Bidgood, Susanna R -- McEwan, William A -- James, Leo C -- 281627/European Research Council/International -- MC_U105181010/Medical Research Council/United Kingdom -- U105181010/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1256070. doi: 10.1126/science.1256070. Epub 2014 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. lcj@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190799" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/*immunology ; Adenovirus Infections, Human/*immunology ; Animals ; Antibodies, Viral/immunology ; Complement C3/*immunology ; Cytokines/biosynthesis/genetics ; Dogs ; HEK293 Cells ; Host-Pathogen Interactions/*immunology ; Humans ; *Immunity, Innate ; Interferon Regulatory Factors/metabolism ; NF-kappa B/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ribonucleoproteins/genetics/metabolism ; Signal Transduction ; Transcription Factor AP-1/metabolism
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bar-Peled, Liron -- New York, N.Y. -- Science. 2014 Dec 5;346(6214):1191-2. doi: 10.1126/science.aaa1808.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Scripps Research Institute, La Jolla, CA 92122, USA. lironbp@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477447" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/*metabolism ; Animals ; *Body Size ; *Cell Enlargement ; *Cell Proliferation ; GTP-Binding Protein Regulators/*metabolism ; Lysosomes/*metabolism ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes/metabolism ; Protein Transport ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
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  • 16
    Publication Date: 2014-01-18
    Description: Transcription factors (TFs) are key players in evolution. Changes affecting their function can yield novel life forms but may also have deleterious effects. Consequently, gene duplication events that release one gene copy from selective pressure are thought to be the common mechanism by which TFs acquire new activities. Here, we show that LEAFY, a major regulator of flower development and cell division in land plants, underwent changes to its DNA binding specificity, even though plant genomes generally contain a single copy of the LEAFY gene. We examined how these changes occurred at the structural level and identify an intermediate LEAFY form in hornworts that appears to adopt all different specificities. This promiscuous intermediate could have smoothed the evolutionary transitions, thereby allowing LEAFY to evolve new binding specificities while remaining a single-copy gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sayou, Camille -- Monniaux, Marie -- Nanao, Max H -- Moyroud, Edwige -- Brockington, Samuel F -- Thevenon, Emmanuel -- Chahtane, Hicham -- Warthmann, Norman -- Melkonian, Michael -- Zhang, Yong -- Wong, Gane Ka-Shu -- Weigel, Detlef -- Parcy, Francois -- Dumas, Renaud -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):645-8. doi: 10.1126/science.1248229. Epub 2014 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS, Laboratoire de Physiologie Cellulaire et Vegetale (LPCV), UMR 5168, 38054 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436181" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis Proteins/chemistry/classification/genetics ; DNA, Plant/*chemistry ; DNA-Binding Proteins/*chemistry/classification/*genetics ; Electrophoretic Mobility Shift Assay ; *Evolution, Molecular ; Gene Dosage ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Proteins/*chemistry/classification/*genetics ; Protein Binding/genetics ; Protein Structure, Tertiary ; Species Specificity ; Transcription Factors/chemistry/classification/genetics
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  • 17
    Publication Date: 2014-08-30
    Description: Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. Similarly, an H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M-containing nucleosomes, and its misregulation in Drosophila results in changes of H3K9 methylation levels and heterochromatic silencing defects. We have established histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508193/" 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/PMC4508193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herz, Hans-Martin -- Morgan, Marc -- Gao, Xin -- Jackson, Jessica -- Rickels, Ryan -- Swanson, Selene K -- Florens, Laurence -- Washburn, Michael P -- Eissenberg, Joel C -- Shilatifard, Ali -- CA R01CA089455/CA/NCI NIH HHS/ -- R01 CA089455/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1065-70. doi: 10.1126/science.1255104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ; Saint Louis University School of Medicine, Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis, MO, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ash@northwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170156" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Chromatin/*metabolism ; Disease Models, Animal ; Drosophila Proteins/genetics ; Drosophila melanogaster ; Gene Silencing ; Glioma/genetics/metabolism ; Heterochromatin/metabolism ; Histone-Lysine N-Methyltransferase/genetics ; Histones/*genetics/metabolism ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Lysine/*genetics ; Methionine/*genetics ; Methylation ; Mutation ; Signal Transduction
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  • 18
    Publication Date: 2014-07-12
    Description: Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naive recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289910/" 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/PMC4289910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carlson, Jonathan M -- Schaefer, Malinda -- Monaco, Daniela C -- Batorsky, Rebecca -- Claiborne, Daniel T -- Prince, Jessica -- Deymier, Martin J -- Ende, Zachary S -- Klatt, Nichole R -- DeZiel, Charles E -- Lin, Tien-Ho -- Peng, Jian -- Seese, Aaron M -- Shapiro, Roger -- Frater, John -- Ndung'u, Thumbi -- Tang, Jianming -- Goepfert, Paul -- Gilmour, Jill -- Price, Matt A -- Kilembe, William -- Heckerman, David -- Goulder, Philip J R -- Allen, Todd M -- Allen, Susan -- Hunter, Eric -- 2P51RR000165-51/RR/NCRR NIH HHS/ -- G108/626/Medical Research Council/United Kingdom -- OD P51OD11132/OD/NIH HHS/ -- P01-AI074415/AI/NIAID NIH HHS/ -- P30 AI050409/AI/NIAID NIH HHS/ -- P51 OD010425/OD/NIH HHS/ -- P51 OD011132/OD/NIH HHS/ -- P51RR165/RR/NCRR NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI64060/AI/NIAID NIH HHS/ -- R37 AI051231/AI/NIAID NIH HHS/ -- R37 AI51231/AI/NIAID NIH HHS/ -- T32 AI007387/AI/NIAID NIH HHS/ -- T32-AI007387/AI/NIAID NIH HHS/ -- U01 AI 66454/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):1254031. doi: 10.1126/science.1254031. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microsoft Research, Redmond, WA 98052, USA. carlson@microsoft.com ehunte4@emory.edu. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. ; Microsoft Research, Redmond, WA 98052, USA. ; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 7BN, UK. National Institute of Health Research, Oxford Biomedical Research Centre, Oxford OX3 7LE, UK. Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany. ; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. ; International AIDS Vaccine Initiative, London SW10 9NH, UK. Imperial College of Science Technology and Medicine, London SW10 9NH, UK. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94105, USA. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. ; Microsoft Research, Los Angeles, CA 98117, USA. ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Microsoft Research, Los Angeles, CA 98117, USA. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. carlson@microsoft.com ehunte4@emory.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013080" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Consensus Sequence ; DNA Mutational Analysis ; Disease Transmission, Infectious/statistics & numerical data ; Female ; HIV Infections/*transmission ; HIV-1/*genetics ; *Heterosexuality ; High-Throughput Nucleotide Sequencing ; Human Immunodeficiency Virus Proteins/genetics ; Humans ; Male ; Models, Statistical ; Molecular Sequence Data ; Point Mutation ; Risk Factors ; *Selection, Genetic ; Viral Load
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  • 19
    Publication Date: 2014-05-17
    Description: Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Uesaka, Naofumi -- Uchigashima, Motokazu -- Mikuni, Takayasu -- Nakazawa, Takanobu -- Nakao, Harumi -- Hirai, Hirokazu -- Aiba, Atsu -- Watanabe, Masahiko -- Kano, Masanobu -- New York, N.Y. -- Science. 2014 May 30;344(6187):1020-3. doi: 10.1126/science.1252514. Epub 2014 May 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. ; Laboratory of Animal Resources, Center for Disease Biology and Integrated Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ; Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. ; Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. mkano-tky@m.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24831527" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/genetics/*metabolism ; Brain/*growth & development/metabolism ; Gene Knockdown Techniques ; Mice ; Mice, Inbred C57BL ; Purkinje Cells/metabolism/*physiology ; RNA Interference ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/genetics/metabolism ; Semaphorin-3A/genetics/*metabolism ; Semaphorins/genetics/*metabolism ; Signal Transduction ; Synapses/genetics/*physiology
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  • 20
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cappellini, Enrico -- Collins, Matthew J -- Gilbert, M Thomas P -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1320-2. doi: 10.1126/science.1249274.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653025" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Databases, Protein ; Fossils ; Humans ; *Mass Spectrometry/instrumentation/methods ; Mummies ; Proteins/*chemistry/isolation & purification ; Proteolysis ; Proteomics
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  • 21
    Publication Date: 2014-11-22
    Description: Chromosome segregation depends on sister chromatid cohesion mediated by cohesin. The cohesin subunits Smc1, Smc3, and Scc1 form tripartite rings that are thought to open at distinct sites to allow entry and exit of DNA. However, direct evidence for the existence of open forms of cohesin is lacking. We found that cohesin's proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. Mutation of this interface abolished cohesin's ability to stably associate with chromatin and to mediate cohesion. Electron microscopy revealed that weakening of the Smc3-Scc1 interface resulted in opening of cohesin rings, as did proteolytic cleavage of Scc1. These open forms may resemble intermediate states of cohesin normally generated by the release factor Wapl and the protease separase, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huis in 't Veld, Pim J -- Herzog, Franz -- Ladurner, Rene -- Davidson, Iain F -- Piric, Sabina -- Kreidl, Emanuel -- Bhaskara, Venugopal -- Aebersold, Ruedi -- Peters, Jan-Michael -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):968-72. doi: 10.1126/science.1256904.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland. Department of Biochemistry, Gene Center, Ludwig-Maximilian University, 81377 Munich, Germany. ; Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule (ETH) Zurich, 8093 Zurich, Switzerland. ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria. peters@imp.ac.at.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25414306" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carrier Proteins/genetics/metabolism ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Chondroitin Sulfate Proteoglycans/chemistry/genetics/*metabolism ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/genetics/*metabolism ; *Chromosome Segregation ; DNA/*metabolism ; DNA Replication ; Humans ; Mass Spectrometry ; Microscopy, Electron ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics/*metabolism ; Phosphoproteins/chemistry/genetics/*metabolism ; Protein Multimerization ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/genetics/metabolism ; Separase/metabolism
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  • 22
    Publication Date: 2014-05-31
    Description: Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4Kbeta (PI4KIIIbeta) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIbeta interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046302/" 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/PMC4046302/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, John E -- Inglis, Alison J -- Perisic, Olga -- Masson, Glenn R -- McLaughlin, Stephen H -- Rutaganira, Florentine -- Shokat, Kevan M -- Williams, Roger L -- MC_U105184308/Medical Research Council/United Kingdom -- PG/11/109/29247/British Heart Foundation/United Kingdom -- PG11/109/29247/British Heart Foundation/United Kingdom -- R01AI099245/AI/NIAID NIH HHS/ -- T32 GM064337/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. jeburke@uvic.ca rlw@mrc-lmb.cam.ac.uk. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876499" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antimalarials/chemistry/pharmacology ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Drug Design ; Humans ; I-kappa B Kinase/*chemistry ; Molecular Sequence Data ; Mutation ; Phosphotransferases (Alcohol Group Acceptor)/*chemistry/genetics ; Plasmodium/drug effects/growth & development ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; rab GTP-Binding Proteins/*chemistry
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  • 23
    Publication Date: 2014-01-05
    Description: Decapentaplegic (Dpp), a Drosophila morphogen signaling protein, transfers directly at synapses made at sites of contact between cells that produce Dpp and cytonemes that extend from recipient cells. The Dpp that cytonemes receive moves together with activated receptors toward the recipient cell body in motile puncta. Genetic loss-of-function conditions for diaphanous, shibire, neuroglian, and capricious perturbed cytonemes by reducing their number or only the synapses they make with cells they target, and reduced cytoneme-mediated transport of Dpp and Dpp signaling. These experiments provide direct evidence that cells use cytonemes to exchange signaling proteins, that cytoneme-based exchange is essential for signaling and normal development, and that morphogen distribution and signaling can be contact-dependent, requiring cytoneme synapses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336149/" 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/PMC4336149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roy, Sougata -- Huang, Hai -- Liu, Songmei -- Kornberg, Thomas B -- GM030637/GM/NIGMS NIH HHS/ -- K99HL114867/HL/NHLBI NIH HHS/ -- R01 GM030637/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):1244624. doi: 10.1126/science.1244624. Epub 2014 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24385607" target="_blank"〉PubMed〈/a〉
    Keywords: Air Sacs/cytology/metabolism ; Animals ; Carrier Proteins/genetics/metabolism ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; *Cell Communication ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*cytology/*metabolism ; Dynamins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Protein Transport ; Pseudopodia/*metabolism ; Signal Transduction ; Trachea/cytology/metabolism
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  • 24
    Publication Date: 2014-03-15
    Description: Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from "slow" to "fast," whose biophysical properties govern the timing, gradation, and amplitude of muscle force. Here we identify the noncanonical Notch ligand Delta-like homolog 1 (Dlk1) as a determinant of motor neuron functional diversification. Dlk1, expressed by ~30% of motor neurons, is necessary and sufficient to promote a fast biophysical signature in the mouse and chick. Dlk1 suppresses Notch signaling and activates expression of the K(+) channel subunit Kcng4 to modulate delayed-rectifier currents. Dlk1 inactivation comprehensively shifts motor neurons toward slow biophysical and transcriptome signatures, while abolishing peak force outputs. Our findings provide insights into the development of motor neuron functional diversity and its contribution to the execution of movements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller, Daniel -- Cherukuri, Pitchaiah -- Henningfeld, Kristine -- Poh, Chor Hoon -- Wittler, Lars -- Grote, Phillip -- Schluter, Oliver -- Schmidt, Jennifer -- Laborda, Jorge -- Bauer, Steven R -- Brownstone, Robert M -- Marquardt, Till -- R01 HD042013/HD/NICHD NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1264-6. doi: 10.1126/science.1246448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Neurobiology Laboratory, European Neuroscience Institute (ENI-G), Grisebachstrasse 5, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626931" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; Intercellular Signaling Peptides and Proteins/genetics/*physiology ; Mice ; Mice, Knockout ; Motor Neurons/*metabolism ; Movement ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/innervation/*physiology ; Potassium Channels, Voltage-Gated/genetics ; Receptors, Notch/*physiology ; Signal Transduction ; Transcriptome
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  • 25
    Publication Date: 2014-01-11
    Description: It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neither an attractant nor a repellent but acts globally as a motogen. Toddler drives internalization of G protein-coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling rescues toddler mutants. These results indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movements, and might be the first in a series of uncharacterized developmental signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107353/" 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/PMC4107353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pauli, Andrea -- Norris, Megan L -- Valen, Eivind -- Chew, Guo-Liang -- Gagnon, James A -- Zimmerman, Steven -- Mitchell, Andrew -- Ma, Jiao -- Dubrulle, Julien -- Reyon, Deepak -- Tsai, Shengdar Q -- Joung, J Keith -- Saghatelian, Alan -- Schier, Alexander F -- K99 HD076935/HD/NICHD NIH HHS/ -- R01 GM056211/GM/NIGMS NIH HHS/ -- R01 GM102491/GM/NIGMS NIH HHS/ -- R01 HG005111/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):1248636. doi: 10.1126/science.1248636. Epub 2014 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24407481" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Cell Movement ; Chemokine CXCL12/metabolism ; Frameshift Mutation ; Gastrulation/genetics/*physiology ; Molecular Sequence Data ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Signal Transduction ; Zebrafish/*embryology/genetics/metabolism ; Zebrafish Proteins/genetics/*metabolism
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  • 26
    Publication Date: 2014-10-18
    Description: Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458378/" 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/PMC4458378/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baud, Matthias G J -- Lin-Shiao, Enrique -- Cardote, Teresa -- Tallant, Cynthia -- Pschibul, Annica -- Chan, Kwok-Ho -- Zengerle, Michael -- Garcia, Jordi R -- Kwan, Terence T-L -- Ferguson, Fleur M -- Ciulli, Alessio -- 097945/Z/11/Z/Wellcome Trust/United Kingdom -- 100476/Z/12/Z/Wellcome Trust/United Kingdom -- BB/G023123/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J001201/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, James Black Centre, Dow Street, Dundee, DD1 5EH, UK. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. a.ciulli@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25323695" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Azepines/chemistry/pharmacology ; Cell Line, Tumor ; Chromatin/chemistry ; Crystallography, X-Ray ; Humans ; Leucine/genetics ; Models, Molecular ; Molecular Probes/*chemistry ; Mutation ; Nuclear Proteins/antagonists & inhibitors/*chemistry/genetics ; Protein Engineering/*methods ; Protein Structure, Tertiary ; Transcription Factors/antagonists & inhibitors/*chemistry/genetics ; Triazoles/chemistry/pharmacology
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  • 27
    Publication Date: 2014-11-29
    Description: T cell responses are initiated by antigen and promoted by a range of costimulatory signals. Understanding how T cells integrate alternative signal combinations and make decisions affecting immune response strength or tolerance poses a considerable theoretical challenge. Here, we report that T cell receptor (TCR) and costimulatory signals imprint an early, cell-intrinsic, division fate, whereby cells effectively count through generations before returning automatically to a quiescent state. This autonomous program can be extended by cytokines. Signals from the TCR, costimulatory receptors, and cytokines add together using a linear division calculus, allowing the strength of a T cell response to be predicted from the sum of the underlying signal components. These data resolve a long-standing costimulation paradox and provide a quantitative paradigm for therapeutically manipulating immune response strength.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marchingo, Julia M -- Kan, Andrey -- Sutherland, Robyn M -- Duffy, Ken R -- Wellard, Cameron J -- Belz, Gabrielle T -- Lew, Andrew M -- Dowling, Mark R -- Heinzel, Susanne -- Hodgkin, Philip D -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1123-7. doi: 10.1126/science.1260044.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. ; Hamilton Institute, National University of Ireland, Maynooth, Ireland. ; Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. The Royal Melbourne Hospital, Parkville, VIC, Australia. ; Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. hodgkin@wehi.edu.au.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430770" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/*immunology ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Cell Division ; Cell Proliferation ; Cytokines/*immunology ; *Immune Tolerance ; Lymphocyte Activation ; Mice ; Receptors, Antigen, T-Cell/*immunology ; Signal Transduction
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  • 28
    Publication Date: 2014-04-20
    Description: Cytoplasmic plant immune receptors recognize specific pathogen effector proteins and initiate effector-triggered immunity. In Arabidopsis, the immune receptors RPS4 and RRS1 are both required to activate defense to three different pathogens. We show that RPS4 and RRS1 physically associate. Crystal structures of the N-terminal Toll-interleukin-1 receptor/resistance (TIR) domains of RPS4 and RRS1, individually and as a heterodimeric complex (respectively at 2.05, 1.75, and 2.65 angstrom resolution), reveal a conserved TIR/TIR interaction interface. We show that TIR domain heterodimerization is required to form a functional RRS1/RPS4 effector recognition complex. The RPS4 TIR domain activates effector-independent defense, which is inhibited by the RRS1 TIR domain through the heterodimerization interface. Thus, RPS4 and RRS1 function as a receptor complex in which the two components play distinct roles in recognition and signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Simon J -- Sohn, Kee Hoon -- Wan, Li -- Bernoux, Maud -- Sarris, Panagiotis F -- Segonzac, Cecile -- Ve, Thomas -- Ma, Yan -- Saucet, Simon B -- Ericsson, Daniel J -- Casey, Lachlan W -- Lonhienne, Thierry -- Winzor, Donald J -- Zhang, Xiaoxiao -- Coerdt, Anne -- Parker, Jane E -- Dodds, Peter N -- Kobe, Bostjan -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):299-303. doi: 10.1126/science.1247357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744375" target="_blank"〉PubMed〈/a〉
    Keywords: Agrobacterium/physiology ; Amino Acid Motifs ; Arabidopsis/chemistry/*immunology/microbiology ; Arabidopsis Proteins/*chemistry/genetics/metabolism ; Bacterial Proteins/immunology/metabolism ; Cell Death ; Crystallography, X-Ray ; Immunity, Innate ; Models, Molecular ; Mutation ; Plant Diseases/immunology/microbiology ; Plant Leaves/microbiology ; Plant Proteins/*chemistry/genetics/metabolism ; Plants, Genetically Modified ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Immunologic/*chemistry/genetics/metabolism ; Signal Transduction ; Tobacco/genetics/immunology/metabolism/microbiology
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  • 29
    Publication Date: 2014-11-22
    Description: Through their association with a kleisin subunit (Scc1), cohesin's Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two alpha helices, forming a four-helix bundle with the coiled coil emerging from Smc3's adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin's association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin's dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300515/" 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/PMC4300515/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gligoris, Thomas G -- Scheinost, Johanna C -- Burmann, Frank -- Petela, Naomi -- Chan, Kok-Lung -- Uluocak, Pelin -- Beckouet, Frederic -- Gruber, Stephan -- Nasmyth, Kim -- Lowe, Jan -- 091859/Z/10/Z/Wellcome Trust/United Kingdom -- 095514/Wellcome Trust/United Kingdom -- 095514/Z/11/Z/Wellcome Trust/United Kingdom -- C573/A 12386/Cancer Research UK/United Kingdom -- C573/A11625/Medical Research Council/United Kingdom -- MC_U105184326/Medical Research Council/United Kingdom -- U10518432/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):963-7. doi: 10.1126/science.1256917.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. ; Max-Planck-Institut fur Biochemie, 82152, Martinsried, Germany. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Medical Research Council (MRC) Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Dunn School of Pathology, University of Oxford, Oxford OX1 3RF, UK. ; Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk. ; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK. kim.nasmyth@bioch.ox.ac.uk jyl@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25414305" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry ; Amino Acid Sequence ; Cell Cycle Proteins/*chemistry/genetics ; Chromosomal Proteins, Non-Histone/*chemistry/genetics ; Conserved Sequence ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; DNA/chemistry ; Mutation ; Protein Multimerization ; Protein Structure, Tertiary ; Saccharomyces cerevisiae Proteins/*chemistry/genetics
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  • 30
    Publication Date: 2014-10-04
    Description: Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified, which constrains them to act as short-range cellular signals. The locality of Wnt signaling dictates that stem cells exiting the Wnt signaling domain differentiate, spatially delimiting the niche in certain tissues. In some instances, stem cells may act as or generate their own niche, enabling the self-organization of patterned tissues. In this Review, we discuss the various ways by which Wnt operates in stem cell control and, in doing so, identify an integral program for tissue renewal and regeneration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clevers, Hans -- Loh, Kyle M -- Nusse, Roel -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):1248012. doi: 10.1126/science.1248012. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht and CancerGenomics.nl, 3584CT Utrecht, Netherlands. ; Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA. ; Department of Developmental Biology, Howard Hughes Medical Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA. rnusse@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/physiology ; Cell Division ; Hair Follicle/physiology ; Humans ; Intestines/physiology ; Mammary Glands, Human/physiology ; Regeneration/genetics/*physiology ; Signal Transduction ; Stem Cell Niche/physiology ; Stem Cells/cytology/metabolism/*physiology ; Transcription, Genetic ; Wnt Proteins/*metabolism
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  • 31
    Publication Date: 2014-04-20
    Description: Most animals sleep more early in life than in adulthood, but the function of early sleep is not known. Using Drosophila, we found that increased sleep in young flies was associated with an elevated arousal threshold and resistance to sleep deprivation. Excess sleep results from decreased inhibition of a sleep-promoting region by a specific dopaminergic circuit. Experimental hyperactivation of this circuit in young flies results in sleep loss and lasting deficits in adult courtship behaviors. These deficits are accompanied by impaired development of a single olfactory glomerulus, VA1v, which normally displays extensive sleep-dependent growth after eclosion. Our results demonstrate that sleep promotes normal brain development that gives rise to an adult behavior critical for species propagation and suggest that rapidly growing regions of the brain are most susceptible to sleep perturbations early in life.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479292/" 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/PMC4479292/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kayser, Matthew S -- Yue, Zhifeng -- Sehgal, Amita -- R25MH060490/MH/NIMH NIH HHS/ -- T32 HL007713/HL/NHLBI NIH HHS/ -- T32HL07713/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):269-74. doi: 10.1126/science.1250553.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744368" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arousal ; Brain/growth & development/physiology ; Courtship ; Dopamine/metabolism ; Dopaminergic Neurons/*physiology ; Drosophila/genetics/growth & development/*physiology ; Female ; Male ; Models, Animal ; Neural Pathways/physiology ; Olfactory Bulb/growth & development/physiology ; Sexual Behavior, Animal ; Signal Transduction ; *Sleep ; Sleep Deprivation ; Temperature
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  • 32
    Publication Date: 2014-07-19
    Description: Unfertilized oocytes have the intrinsic capacity to remodel sperm and the nuclei of somatic cells. The discoveries that cells can change their phenotype from differentiated to embryonic state using oocytes or specific transcription factors have been recognized as two major breakthroughs in the biomedical field. Here, we show that ASF1A, a histone-remodeling chaperone specifically enriched in the metaphase II human oocyte, is necessary for reprogramming of human adult dermal fibroblasts (hADFs) into undifferentiated induced pluripotent stem cell. We also show that overexpression of just ASF1A and OCT4 in hADFs exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells. Our Report underscores the importance of studying the unfertilized MII oocyte as a means to understand the molecular pathways governing somatic cell reprogramming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez-Munoz, Elena -- Arboleda-Estudillo, Yohanna -- Otu, Hasan H -- Cibelli, Jose B -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):822-5. doi: 10.1126/science.1254745. Epub 2014 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉LARCEL, Laboratorio Andaluz de Reprogramacion Celular, BIONAND, Centro Andaluz de Nanomedicina y Biotecnologia Andalucia, 29590, Spain. ; Department of Genetics and Bioengineering, Istanbul Bilgi University 34060, Istanbul, Turkey. Department of Electrical Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA. ; LARCEL, Laboratorio Andaluz de Reprogramacion Celular, BIONAND, Centro Andaluz de Nanomedicina y Biotecnologia Andalucia, 29590, Spain. Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA. Department of Physiology, Michigan State University, East Lansing, MI 48824, USA. cibelli@msu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035411" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Cell Cycle Proteins/genetics/*metabolism ; Cell Dedifferentiation ; Cell Differentiation ; *Cellular Reprogramming ; Embryonic Stem Cells/cytology/physiology ; Fibroblasts/cytology/physiology ; Growth Differentiation Factor 9/metabolism ; Histone Chaperones/genetics/*metabolism ; Histones/metabolism ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Metaphase ; Octamer Transcription Factor-3/metabolism ; Oocytes/cytology/physiology ; Signal Transduction ; Transcriptional Activation ; Transcriptome
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  • 33
    Publication Date: 2014-10-25
    Description: Cellular circuits sense the environment, process signals, and compute decisions using networks of interacting proteins. To model such a system, the abundance of each activated protein species can be described as a stochastic function of the abundance of other proteins. High-dimensional single-cell technologies, such as mass cytometry, offer an opportunity to characterize signaling circuit-wide. However, the challenge of developing and applying computational approaches to interpret such complex data remains. Here, we developed computational methods, based on established statistical concepts, to characterize signaling network relationships by quantifying the strengths of network edges and deriving signaling response functions. In comparing signaling between naive and antigen-exposed CD4(+) T lymphocytes, we find that although these two cell subtypes had similarly wired networks, naive cells transmitted more information along a key signaling cascade than did antigen-exposed cells. We validated our characterization on mice lacking the extracellular-regulated mitogen-activated protein kinase (MAPK) ERK2, which showed stronger influence of pERK on pS6 (phosphorylated-ribosomal protein S6), in naive cells as compared with antigen-exposed cells, as predicted. We demonstrate that by using cell-to-cell variation inherent in single-cell data, we can derive response functions underlying molecular circuits and drive the understanding of how cells process signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334155/" 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/PMC4334155/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krishnaswamy, Smita -- Spitzer, Matthew H -- Mingueneau, Michael -- Bendall, Sean C -- Litvin, Oren -- Stone, Erica -- Pe'er, Dana -- Nolan, Garry P -- 1K01DK095008/DK/NIDDK NIH HHS/ -- 1R01CA130826/CA/NCI NIH HHS/ -- 1U54CA121852-01A1/CA/NCI NIH HHS/ -- CA 09-011/CA/NCI NIH HHS/ -- HHSN268201000034C/HV/NHLBI NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HV-10-05/HV/NHLBI NIH HHS/ -- K01 DK095008/DK/NIDDK NIH HHS/ -- P01 CA034233/CA/NCI NIH HHS/ -- R00 GM104148/GM/NIGMS NIH HHS/ -- R01 CA130826/CA/NCI NIH HHS/ -- S10RR027582-01/RR/NCRR NIH HHS/ -- U19 AI057229/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 CA149145/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1250689. doi: 10.1126/science.1250689. Epub 2014 Oct 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA. ; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA. ; Molecular Biology Section, Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. ; Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, NY, USA. dpeer@biology.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25342659" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology ; Computer Simulation ; Image Cytometry ; Male ; Mice ; Mice, Mutant Strains ; Mitogen-Activated Protein Kinase 1/genetics ; Receptors, Antigen, T-Cell/*metabolism ; Ribosomal Protein S6/metabolism ; Signal Transduction ; Single-Cell Analysis/*methods ; Systems Biology/*methods ; eIF-2 Kinase/metabolism
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  • 34
    Publication Date: 2014-03-01
    Description: Auxin-binding protein 1 (ABP1) was discovered nearly 40 years ago and was shown to be essential for plant development and morphogenesis, but its mode of action remains unclear. Here, we report that the plasma membrane-localized transmembrane kinase (TMK) receptor-like kinases interact with ABP1 and transduce auxin signal to activate plasma membrane-associated ROPs [Rho-like guanosine triphosphatases (GTPase) from plants], leading to changes in the cytoskeleton and the shape of leaf pavement cells in Arabidopsis. The interaction between ABP1 and TMK at the cell surface is induced by auxin and requires ABP1 sensing of auxin. These findings show that TMK proteins and ABP1 form a cell surface auxin perception complex that activates ROP signaling pathways, regulating nontranscriptional cytoplasmic responses and associated fundamental processes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166562/" 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/PMC4166562/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Tongda -- Dai, Ning -- Chen, Jisheng -- Nagawa, Shingo -- Cao, Min -- Li, Hongjiang -- Zhou, Zimin -- Chen, Xu -- De Rycke, Riet -- Rakusova, Hana -- Wang, Wuyi -- Jones, Alan M -- Friml, Jiri -- Patterson, Sara E -- Bleecker, Anthony B -- Yang, Zhenbiao -- GM065989/GM/NIGMS NIH HHS/ -- GM081451/GM/NIGMS NIH HHS/ -- R01 GM081451/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 28;343(6174):1025-8. doi: 10.1126/science.1245125.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Plant Cell Biology, Department of Botany and Plant Sciences, University of California, Riverside, CA 92521, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24578577" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*enzymology/genetics ; Cell Membrane/*enzymology ; Indoleacetic Acids/*metabolism ; Plant Leaves/enzymology/genetics ; Plant Proteins/*metabolism ; Protein Kinases/genetics/*metabolism ; Receptors, Cell Surface/*metabolism ; Signal Transduction ; rho GTP-Binding Proteins/*metabolism
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  • 35
    Publication Date: 2014-12-20
    Description: Evolution and design of protein complexes are almost always viewed through the lens of amino acid mutations at protein interfaces. We showed previously that residues not involved in the physical interaction between proteins make important contributions to oligomerization by acting indirectly or allosterically. In this work, we sought to investigate the mechanism by which allosteric mutations act, using the example of the PyrR family of pyrimidine operon attenuators. In this family, a perfectly sequence-conserved helix that forms a tetrameric interface is exposed as solvent-accessible surface in dimeric orthologs. This means that mutations must be acting from a distance to destabilize the interface. We identified 11 key mutations controlling oligomeric state, all distant from the interfaces and outside ligand-binding pockets. Finally, we show that the key mutations introduce conformational changes equivalent to the conformational shift between the free versus nucleotide-bound conformations of the proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337988/" 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/PMC4337988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perica, Tina -- Kondo, Yasushi -- Tiwari, Sandhya P -- McLaughlin, Stephen H -- Kemplen, Katherine R -- Zhang, Xiuwei -- Steward, Annette -- Reuter, Nathalie -- Clarke, Jane -- Teichmann, Sarah A -- 095195/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1254346. doi: 10.1126/science.1254346.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Department of Molecular Biology, University of Bergen University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. Computational Biology Unit, Department of Informatics, University of Bergen, P.O. Box 7803, N-5020 Bergen, Norway. ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. saraht@ebi.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525255" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation/*genetics ; Amino Acid Sequence ; Bacillus subtilis/metabolism ; Bacterial Proteins/*chemistry/genetics ; Conserved Sequence ; *Evolution, Molecular ; Ligands ; Mutation ; Pentosyltransferases/*chemistry/genetics ; Protein Binding/genetics ; Protein Conformation ; *Protein Engineering ; Protein Multimerization/*genetics ; Repressor Proteins/*chemistry/genetics
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  • 36
    Publication Date: 2014-01-18
    Description: Btk29A is the Drosophila ortholog of the mammalian Bruton's tyrosine kinase (Btk), mutations of which in humans cause a heritable immunodeficiency disease. Btk29A mutations stabilized the proliferating cystoblast fate, leading to an ovarian tumor. This phenotype was rescued by overexpression of wild-type Btk29A and phenocopied by the interference of Wnt4-beta-catenin signaling or its putative downstream nuclear protein Piwi in somatic escort cells. Btk29A and mammalian Btk directly phosphorylated tyrosine residues of beta-catenin, leading to the up-regulation of its transcriptional activity. Thus, we identify a transcriptional switch involving the kinase Btk29A/Btk and its phosphorylation target, beta-catenin, which functions downstream of Wnt4 in escort cells to terminate Drosophila germ cell proliferation through up-regulation of piwi expression. This signaling mechanism likely represents a versatile developmental switch.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamada-Kawaguchi, Noriko -- Nore, Beston F -- Kuwada, Yusuke -- Smith, C I Edvard -- Yamamoto, Daisuke -- New York, N.Y. -- Science. 2014 Jan 17;343(6168):294-7. doi: 10.1126/science.1244512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology and Neurosciences, Tohoku University Graduate School of Life Sciences, Sendai 980-8577, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24436419" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins/*biosynthesis ; *Cell Proliferation ; DNA Breaks, Double-Stranded ; Drosophila Proteins/*biosynthesis/genetics/*metabolism ; Drosophila melanogaster/genetics/metabolism/*physiology ; Gene Knockdown Techniques ; Genomic Instability ; Germ Cells/cytology/metabolism/*physiology ; Glycoproteins/genetics/*metabolism ; Phosphorylation ; Protein-Tyrosine Kinases/genetics/*metabolism ; RNA, Small Interfering/genetics/metabolism ; Signal Transduction ; Transcription, Genetic ; Tyrosine/genetics/metabolism ; Up-Regulation ; Wnt Proteins/genetics/*metabolism ; beta Catenin/genetics/*metabolism
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  • 37
    Publication Date: 2014-04-20
    Description: Tight junctions are cell-cell adhesion structures in epithelial cell sheets that surround organ compartments in multicellular organisms and regulate the permeation of ions through the intercellular space. Claudins are the major constituents of tight junctions and form strands that mediate cell adhesion and function as paracellular barriers. We report the structure of mammalian claudin-15 at a resolution of 2.4 angstroms. The structure reveals a characteristic beta-sheet fold comprising two extracellular segments, which is anchored to a transmembrane four-helix bundle by a consensus motif. Our analyses suggest potential paracellular pathways with distinctive charges on the extracellular surface, providing insight into the molecular basis of ion homeostasis across tight junctions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Hiroshi -- Nishizawa, Tomohiro -- Tani, Kazutoshi -- Yamazaki, Yuji -- Tamura, Atsushi -- Ishitani, Ryuichiro -- Dohmae, Naoshi -- Tsukita, Sachiko -- Nureki, Osamu -- Fujiyoshi, Yoshinori -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):304-7. doi: 10.1126/science.1248571.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744376" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Claudins/*chemistry ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Static Electricity ; Tight Junctions/*chemistry/physiology
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  • 38
    Publication Date: 2014-04-26
    Description: Light is a source of energy and also a regulator of plant physiological adaptations. We show here that light/dark conditions affect alternative splicing of a subset of Arabidopsis genes preferentially encoding proteins involved in RNA processing. The effect requires functional chloroplasts and is also observed in roots when the communication with the photosynthetic tissues is not interrupted, suggesting that a signaling molecule travels through the plant. Using photosynthetic electron transfer inhibitors with different mechanisms of action, we deduce that the reduced pool of plastoquinones initiates a chloroplast retrograde signaling that regulates nuclear alternative splicing and is necessary for proper plant responses to varying light conditions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382720/" 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/PMC4382720/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petrillo, Ezequiel -- Godoy Herz, Micaela A -- Fuchs, Armin -- Reifer, Dominik -- Fuller, John -- Yanovsky, Marcelo J -- Simpson, Craig -- Brown, John W S -- Barta, Andrea -- Kalyna, Maria -- Kornblihtt, Alberto R -- BB/G024979/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- P 26333/Austrian Science Fund FWF/Austria -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 25;344(6182):427-30. doi: 10.1126/science.1250322. Epub 2014 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratorio de Fisiologia y Biologia Molecular, Departamento de Fisiologia, Biologia Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellon 2, C1428EHA Buenos Aires, Argentina.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24763593" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Cell Nucleus/genetics ; Chloroplasts/*metabolism ; Circadian Clocks ; Dibromothymoquinone/pharmacology ; Diuron/pharmacology ; Electron Transport/drug effects ; *Gene Expression Regulation, Plant ; Light ; Models, Biological ; Oxidation-Reduction ; Photosynthesis/drug effects ; Plant Leaves/metabolism ; Plant Roots/metabolism ; Plants, Genetically Modified ; Plastoquinone/*metabolism ; RNA Stability ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Seedlings/genetics/metabolism ; Signal Transduction
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  • 39
    Publication Date: 2014-08-16
    Description: Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zuryn, Steven -- Ahier, Arnaud -- Portoso, Manuela -- White, Esther Redhouse -- Morin, Marie-Charlotte -- Margueron, Raphael -- Jarriault, Sophie -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):826-9. doi: 10.1126/science.1255885.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Development and Stem Cells, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Universite de Strasbourg, 67404 Illkirch CU Strasbourg, France. ; Institut Curie, INSERM U934, CNRS UMR3215, 26, Rue d'Ulm, 75005 Paris, France. ; Department of Development and Stem Cells, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS UMR 7104/INSERM U964, Universite de Strasbourg, 67404 Illkirch CU Strasbourg, France. sophie@igbmc.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124442" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/*cytology/genetics ; Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism ; Cell Dedifferentiation ; Cell Nucleus/metabolism/ultrastructure ; *Cell Transdifferentiation ; Digestive System/cytology ; Histone Demethylases/chemistry/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/genetics/*metabolism ; Histones/*metabolism ; Lysine/metabolism ; Methylation ; Models, Biological ; Molecular Sequence Data ; Motor Neurons/*cytology ; Transcription Factors/metabolism
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  • 40
    Publication Date: 2014-12-17
    Description: Iron sequestration provides an innate defense, termed nutritional immunity, leading pathogens to scavenge iron from hosts. Although the molecular basis of this battle for iron is established, its potential as a force for evolution at host-pathogen interfaces is unknown. We show that the iron transport protein transferrin is engaged in ancient and ongoing evolutionary conflicts with TbpA, a transferrin surface receptor from bacteria. Single substitutions in transferrin at rapidly evolving sites reverse TbpA binding, providing a mechanism to counteract bacterial iron piracy among great apes. Furthermore, the C2 transferrin polymorphism in humans evades TbpA variants from Haemophilus influenzae, revealing a functional basis for standing genetic variation. These findings identify a central role for nutritional immunity in the persistent evolutionary conflicts between primates and bacterial pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455941/" 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/PMC4455941/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barber, Matthew F -- Elde, Nels C -- 1F32GM108288/GM/NIGMS NIH HHS/ -- GM090042/GM/NIGMS NIH HHS/ -- R00 GM090042/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1362-6. doi: 10.1126/science.1259329.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. nelde@genetics.utah.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504720" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Evolution, Molecular ; Haemophilus influenzae/*metabolism ; Haplorhini/*genetics/immunology/*metabolism ; Humans ; Immunity, Innate ; Models, Molecular ; Molecular Sequence Data ; Neisseria/*metabolism ; Neisseria gonorrhoeae/metabolism ; Neisseria meningitidis/metabolism ; Phylogeny ; Polymorphism, Genetic ; Protein Binding ; Selection, Genetic ; Transferrin/chemistry/*genetics/*metabolism ; Transferrin-Binding Protein A/chemistry/*genetics/*metabolism
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  • 41
    Publication Date: 2014-06-21
    Description: Primate lentiviruses exhibit narrow host tropism, reducing the occurrence of zoonoses but also impairing the development of optimal animal models of AIDS. To delineate the factors limiting cross-species HIV-1 transmission, we passaged a modified HIV-1 in pigtailed macaques that were transiently depleted of CD8(+) cells during acute infection. During adaptation over four passages in macaques, HIV-1 acquired the ability to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels, and ultimately caused marked CD4(+) T cell depletion and AIDS-defining conditions. Transient treatment with an antibody to CD8 during acute HIV-1 infection caused rapid progression to AIDS, whereas untreated animals exhibited an elite controller phenotype. Thus, an adapted HIV-1 can cause AIDS in macaques, and stark differences in outcome can be determined by immunological perturbations during early infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266393/" 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/PMC4266393/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hatziioannou, Theodora -- Del Prete, Gregory Q -- Keele, Brandon F -- Estes, Jacob D -- McNatt, Matthew W -- Bitzegeio, Julia -- Raymond, Alice -- Rodriguez, Anthony -- Schmidt, Fabian -- Mac Trubey, C -- Smedley, Jeremy -- Piatak, Michael Jr -- KewalRamani, Vineet N -- Lifson, Jeffrey D -- Bieniasz, Paul D -- HHSN261200800001E/PHS HHS/ -- R01 AI050111/AI/NIAID NIH HHS/ -- R01 AI078788/AI/NIAID NIH HHS/ -- R01AI078788/AI/NIAID NIH HHS/ -- R01AI50111/AI/NIAID NIH HHS/ -- R37 AI064003/AI/NIAID NIH HHS/ -- R37AI64003/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1401-5. doi: 10.1126/science.1250761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. ; Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. ; Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. ; Laboratory Animal Sciences Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. ; HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org. ; Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. Howard Hughes Medical Institute, 455 First Avenue, New York, NY 10016, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24948736" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/immunology/transmission/*virology ; Amino Acid Sequence ; Animals ; Antigens, CD8/immunology ; CD4-Positive T-Lymphocytes/immunology ; *Disease Models, Animal ; HIV-1/genetics/*physiology ; Host-Pathogen Interactions/*immunology ; Human Immunodeficiency Virus Proteins/chemistry/genetics/metabolism ; Lymphocyte Depletion ; Macaca nemestrina/immunology/*virology ; Molecular Sequence Data ; Protein Structure, Tertiary ; Viral Regulatory and Accessory Proteins/chemistry/genetics/metabolism ; Virus Replication
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  • 42
    Publication Date: 2014-03-22
    Description: Under resting conditions, Pink1 knockout cells and cells derived from patients with PINK1 mutations display a loss of mitochondrial complex I reductive activity, causing a decrease in the mitochondrial membrane potential. Analyzing the phosphoproteome of complex I in liver and brain from Pink1(-/-) mice, we found specific loss of phosphorylation of serine-250 in complex I subunit NdufA10. Phosphorylation of serine-250 was needed for ubiquinone reduction by complex I. Phosphomimetic NdufA10 reversed Pink1 deficits in mouse knockout cells and rescued mitochondrial depolarization and synaptic transmission defects in pink(B9)-null mutant Drosophila. Complex I deficits and adenosine triphosphate synthesis were also rescued in cells derived from PINK1 patients. Thus, this evolutionary conserved pathway may contribute to the pathogenic cascade that eventually leads to Parkinson's disease in patients with PINK1 mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morais, Vanessa A -- Haddad, Dominik -- Craessaerts, Katleen -- De Bock, Pieter-Jan -- Swerts, Jef -- Vilain, Sven -- Aerts, Liesbeth -- Overbergh, Lut -- Grunewald, Anne -- Seibler, Philip -- Klein, Christine -- Gevaert, Kris -- Verstreken, Patrik -- De Strooper, Bart -- New York, N.Y. -- Science. 2014 Apr 11;344(6180):203-7. doi: 10.1126/science.1249161. Epub 2014 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉VIB Center for the Biology of Disease, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24652937" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Brain/enzymology ; Drosophila Proteins/*metabolism ; Electron Transport Complex I/*metabolism ; Humans ; Liver/enzymology ; Membrane Potential, Mitochondrial/genetics ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; NADH Dehydrogenase/*metabolism ; Parkinson Disease/*enzymology/*genetics ; Phosphorylation/genetics ; Protein Kinases/*genetics ; Proteome ; Serine/chemistry/metabolism
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  • 43
    Publication Date: 2014-05-17
    Description: Signaling from JAK (Janus kinase) protein kinases to STAT (signal transducers and activators of transcription) transcription factors is key to many aspects of biology and medicine, yet the mechanism by which cytokine receptors initiate signaling is enigmatic. We present a complete mechanistic model for activation of receptor-bound JAK2, based on an archetypal cytokine receptor, the growth hormone receptor. For this, we used fluorescence resonance energy transfer to monitor positioning of the JAK2 binding motif in the receptor dimer, substitution of the receptor extracellular domains with Jun zippers to control the position of its transmembrane (TM) helices, atomistic modeling of TM helix movements, and docking of the crystal structures of the JAK2 kinase and its inhibitory pseudokinase domain with an opposing kinase-pseudokinase domain pair. Activation of the receptor dimer induced a separation of its JAK2 binding motifs, driven by a ligand-induced transition from a parallel TM helix pair to a left-handed crossover arrangement. This separation leads to removal of the pseudokinase domain from the kinase domain of the partner JAK2 and pairing of the two kinase domains, facilitating trans-activation. This model may well generalize to other class I cytokine receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooks, Andrew J -- Dai, Wei -- O'Mara, Megan L -- Abankwa, Daniel -- Chhabra, Yash -- Pelekanos, Rebecca A -- Gardon, Olivier -- Tunny, Kathryn A -- Blucher, Kristopher M -- Morton, Craig J -- Parker, Michael W -- Sierecki, Emma -- Gambin, Yann -- Gomez, Guillermo A -- Alexandrov, Kirill -- Wilson, Ian A -- Doxastakis, Manolis -- Mark, Alan E -- Waters, Michael J -- New York, N.Y. -- Science. 2014 May 16;344(6185):1249783. doi: 10.1126/science.1249783.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. m.waters@uq.edu.au a.brooks@uq.edu.au. ; Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77004, USA. ; The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. ; Biota Structural Biology Laboratory and Australian Cancer Research Foundation (ACRF) Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Department of Biochemistry and Molecular Biology and Bio21 Institute, University of Melbourne, Parkville, Victoria 3052, Australia. ; Scripps Research Institute, La Jolla, CA 92037, USA. ; The University of Queensland, Institute for Molecular Bioscience (IMB), St Lucia, Queensland 4072, Australia. The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia, Queensland 4072, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833397" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Cysteine/chemistry ; Enzyme Activation ; HEK293 Cells ; Humans ; Janus Kinase 2/antagonists & inhibitors/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Somatotropin/chemistry/genetics/*metabolism
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  • 44
    Publication Date: 2014-02-18
    Description: In this work, we investigate morphological differences between Arabidopsis thaliana, which has simple leaves, and its relative Cardamine hirsuta, which has dissected leaves comprising distinct leaflets. With the use of genetics, interspecific gene transfers, and time-lapse imaging, we show that leaflet development requires the REDUCED COMPLEXITY (RCO) homeodomain protein. RCO functions specifically in leaves, where it sculpts developing leaflets by repressing growth at their flanks. RCO evolved in the Brassicaceae family through gene duplication and was lost in A. thaliana, contributing to leaf simplification in this species. Species-specific RCO action with respect to its paralog results from its distinct gene expression pattern in the leaf base. Thus, regulatory evolution coupled with gene duplication and loss generated leaf shape diversity by modifying local growth patterns during organogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vlad, Daniela -- Kierzkowski, Daniel -- Rast, Madlen I -- Vuolo, Francesco -- Dello Ioio, Raffaele -- Galinha, Carla -- Gan, Xiangchao -- Hajheidari, Mohsen -- Hay, Angela -- Smith, Richard S -- Huijser, Peter -- Bailey, C Donovan -- Tsiantis, Miltos -- BB/H006974/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/H011455/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):780-3. doi: 10.1126/science.1248384.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531971" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/anatomy & histology/genetics ; Brassicaceae/*anatomy & histology/*genetics ; Chromosome Mapping ; *Evolution, Molecular ; Gene Duplication ; *Gene Expression Regulation, Plant ; *Genes, Homeobox ; Genetic Complementation Test ; Molecular Sequence Data ; Plant Leaves/*anatomy & histology/*genetics
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  • 45
    Publication Date: 2014-05-09
    Description: Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases, including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an "alternatively activated" phenotype. TAM terminal differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204732/" 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/PMC4204732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Franklin, Ruth A -- Liao, Will -- Sarkar, Abira -- Kim, Myoungjoo V -- Bivona, Michael R -- Liu, Kang -- Pamer, Eric G -- Li, Ming O -- AI101251/AI/NIAID NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 AI101251/AI/NIAID NIH HHS/ -- R37 AI039031/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 May 23;344(6186):921-5. doi: 10.1126/science.1252510. Epub 2014 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA. ; New York Genome Center, New York, NY 10022, USA. ; Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. ; Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA. ; Immunology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. lim@mskcc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812208" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Female ; Inflammation/immunology/pathology ; Macrophages/*immunology ; Mammary Neoplasms, Animal/*immunology/*pathology ; Mice ; Mice, Inbred C57BL ; Monocyte-Macrophage Precursor Cells/immunology ; Receptors, Notch/metabolism ; Signal Transduction ; Vascular Cell Adhesion Molecule-1/metabolism
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  • 46
    Publication Date: 2014-03-15
    Description: Histone variants have been proposed to act as determinants for posttranslational modifications with widespread regulatory functions. We identify a histone-modifying enzyme that selectively methylates the replication-dependent histone H3 variant H3.1. The crystal structure of the SET domain of the histone H3 lysine-27 (H3K27) methyltransferase ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) in complex with a H3.1 peptide shows that ATXR5 contains a bipartite catalytic domain that specifically "reads" alanine-31 of H3.1. Variation at position 31 between H3.1 and replication-independent H3.3 is conserved in plants and animals, and threonine-31 in H3.3 is responsible for inhibiting the activity of ATXR5 and its paralog, ATXR6. Our results suggest a simple model for the mitotic inheritance of the heterochromatic mark H3K27me1 and the protection of H3.3-enriched genes against heterochromatization during DNA replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049228/" 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/PMC4049228/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacob, Yannick -- Bergamin, Elisa -- Donoghue, Mark T A -- Mongeon, Vanessa -- LeBlanc, Chantal -- Voigt, Philipp -- Underwood, Charles J -- Brunzelle, Joseph S -- Michaels, Scott D -- Reinberg, Danny -- Couture, Jean-Francois -- Martienssen, Robert A -- BMA-355900/Canadian Institutes of Health Research/Canada -- GM064844/GM/NIGMS NIH HHS/ -- GM067014/GM/NIGMS NIH HHS/ -- GM075060/GM/NIGMS NIH HHS/ -- R01 GM067014/GM/NIGMS NIH HHS/ -- R01 GM075060/GM/NIGMS NIH HHS/ -- R37 GM037120/GM/NIGMS NIH HHS/ -- R37GM037120/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1249-53. doi: 10.1126/science.1248357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24626927" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/*chemistry/metabolism ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; DNA Replication ; Epigenesis, Genetic ; Gene Expression Regulation, Plant ; Heterochromatin/*metabolism ; Histones/*metabolism ; Methylation ; Methyltransferases/*chemistry/metabolism ; Mitosis ; Molecular Sequence Data ; *Protein Processing, Post-Translational ; Threonine/metabolism
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  • 47
    Publication Date: 2014-06-28
    Description: Lassa virus spreads from a rodent to humans and can lead to lethal hemorrhagic fever. Despite its broad tropism, chicken cells were reported 30 years ago to resist infection. We found that Lassa virus readily engaged its cell-surface receptor alpha-dystroglycan in avian cells, but virus entry in susceptible species involved a pH-dependent switch to an intracellular receptor, the lysosome-resident protein LAMP1. Iterative haploid screens revealed that the sialyltransferase ST3GAL4 was required for the interaction of the virus glycoprotein with LAMP1. A single glycosylated residue in LAMP1, present in susceptible species but absent in birds, was essential for interaction with the Lassa virus envelope protein and subsequent infection. The resistance of Lamp1-deficient mice to Lassa virus highlights the relevance of this receptor switch in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239993/" 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/PMC4239993/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jae, Lucas T -- Raaben, Matthijs -- Herbert, Andrew S -- Kuehne, Ana I -- Wirchnianski, Ariel S -- Soh, Timothy K -- Stubbs, Sarah H -- Janssen, Hans -- Damme, Markus -- Saftig, Paul -- Whelan, Sean P -- Dye, John M -- Brummelkamp, Thijn R -- AI081842/AI/NIAID NIH HHS/ -- AI109740/AI/NIAID NIH HHS/ -- R01 AI081842/AI/NIAID NIH HHS/ -- T32 AI007245/AI/NIAID NIH HHS/ -- U19 AI109740/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1506-10. doi: 10.1126/science.1252480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. ; Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. ; U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. ; Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. ; Biochemisches Institut, Christian Albrechts-Universitat Kiel, 24118 Kiel, Germany. ; Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu. ; U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu. ; Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Cancer Genomics Center (CGC.nl), Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970085" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/metabolism/virology ; Cells, Cultured ; Chickens ; Dystroglycans/genetics/metabolism ; Glycosylation ; Humans ; Hydrogen-Ion Concentration ; Lassa Fever/virology ; Lassa virus/*physiology ; Lysosomal-Associated Membrane Protein 1/chemistry/*metabolism ; Lysosomes/metabolism/virology ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Protein Binding ; Receptors, Virus/*metabolism ; Sialyltransferases/metabolism ; Viral Envelope Proteins/*metabolism ; *Virus Internalization
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  • 48
    Publication Date: 2014-03-22
    Description: The 18-kilodalton translocator protein TSPO is found in mitochondrial membranes and mediates the import of cholesterol and porphyrins into mitochondria. In line with the role of TSPO in mitochondrial function, TSPO ligands are used for a variety of diagnostic and therapeutic applications in animals and humans. We present the three-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of five transmembrane alpha helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggests a molecular mechanism for the stimulation of cholesterol transport into mitochondria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaremko, Lukasz -- Jaremko, Mariusz -- Giller, Karin -- Becker, Stefan -- Zweckstetter, Markus -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur Biophysikalische Chemie, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653034" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Biological Transport ; Cholesterol/metabolism ; Hydrophobic and Hydrophilic Interactions ; Isoquinolines/*chemistry/metabolism ; Ligands ; Mice ; Micelles ; Mitochondria/metabolism ; Mitochondrial Membrane Transport Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, GABA/*chemistry/metabolism ; Recombinant Proteins/chemistry/metabolism
    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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  • 49
    Publication Date: 2014-06-07
    Description: Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157056/" 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/PMC4157056/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Yu -- Xie, Min -- Chen, Wenbin -- Talbot, Richard -- Maddox, Jillian F -- Faraut, Thomas -- Wu, Chunhua -- Muzny, Donna M -- Li, Yuxiang -- Zhang, Wenguang -- Stanton, Jo-Ann -- Brauning, Rudiger -- Barris, Wesley C -- Hourlier, Thibaut -- Aken, Bronwen L -- Searle, Stephen M J -- Adelson, David L -- Bian, Chao -- Cam, Graham R -- Chen, Yulin -- Cheng, Shifeng -- DeSilva, Udaya -- Dixen, Karen -- Dong, Yang -- Fan, Guangyi -- Franklin, Ian R -- Fu, Shaoyin -- Fuentes-Utrilla, Pablo -- Guan, Rui -- Highland, Margaret A -- Holder, Michael E -- Huang, Guodong -- Ingham, Aaron B -- Jhangiani, Shalini N -- Kalra, Divya -- Kovar, Christie L -- Lee, Sandra L -- Liu, Weiqing -- Liu, Xin -- Lu, Changxin -- Lv, Tian -- Mathew, Tittu -- McWilliam, Sean -- Menzies, Moira -- Pan, Shengkai -- Robelin, David -- Servin, Bertrand -- Townley, David -- Wang, Wenliang -- Wei, Bin -- White, Stephen N -- Yang, Xinhua -- Ye, Chen -- Yue, Yaojing -- Zeng, Peng -- Zhou, Qing -- Hansen, Jacob B -- Kristiansen, Karsten -- Gibbs, Richard A -- Flicek, Paul -- Warkup, Christopher C -- Jones, Huw E -- Oddy, V Hutton -- Nicholas, Frank W -- McEwan, John C -- Kijas, James W -- Wang, Jun -- Worley, Kim C -- Archibald, Alan L -- Cockett, Noelle -- Xu, Xun -- Wang, Wen -- Dalrymple, Brian P -- 095908/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- BB/1025360/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025328/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025360/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025506/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- U54 HG003273/HG/NHGRI NIH HHS/ -- WT095908/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1168-73. doi: 10.1126/science.1252806.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. ; BGI-Shenzhen, Shenzhen 518083, China. ; Ediburgh Genomics, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. ; Utah State University, Logan, UT 84322-4815, USA. ; Institut National de la Recherche Agronomique, Laboratoire de Genetique Cellulaire, UMR 444, Castanet-Tolosan F-31326, France. ; Utah State University, Logan, UT 84322-1435, USA. ; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Inner Mongolia Agricultural University, Hohhot 010018, China. Institute of ATCG, Nei Mongol Bio-Information, Hohhot, China. ; Department of Anatomy, University of Otago, Dunedin 9054, New Zealand. ; AgResearch, Invermay Agricultural Centre, Mosgiel 9053, New Zealand. ; Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. ; Department of Biology, University of Copenhagen, DK-2100 Copenhagen O, Denmark. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. ; Inner Mongolia Agricultural University, Hohhot 010018, China. ; U.S. Department of Agriculture Agricultural Research Service Animal Disease Research Unit, Pullman, WA 99164, USA. Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA. ; BGI-Shenzhen, Shenzhen 518083, China. Maize Research Institute, Sichuan Agricultural University, Chengdu 611130, China. ; Lanzhou Institute of Husbandry and Pharmaceutical Science, Lanzhou, 730050, China. ; Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark. ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; Biosciences Knowledge Transfer Network, The Roslin Institute, Easter Bush, Midlothian, EH25 9RG, UK. ; School of Environmental and Rural Science, University of New England, Armidale, NSW 2351, Australia. ; Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia. ; BGI-Shenzhen, Shenzhen 518083, China. Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Macau University of Science and Technology, Macau 999078, China. ; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; Utah State University, Logan, UT 84322-1435, USA. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; BGI-Shenzhen, Shenzhen 518083, China. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904168" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Fatty Acids, Volatile/metabolism/physiology ; Gene Expression Regulation ; Genome ; Keratins, Hair-Specific/genetics ; Lipid Metabolism/genetics/*physiology ; Molecular Sequence Data ; Phylogeny ; Rumen/metabolism/*physiology ; Sheep, Domestic/classification/*genetics/*metabolism ; Transcriptome ; Wool/growth & development
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  • 50
    Publication Date: 2014-02-08
    Description: Type II CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems use an RNA-guided DNA endonuclease, Cas9, to generate double-strand breaks in invasive DNA during an adaptive bacterial immune response. Cas9 has been harnessed as a powerful tool for genome editing and gene regulation in many eukaryotic organisms. We report 2.6 and 2.2 angstrom resolution crystal structures of two major Cas9 enzyme subtypes, revealing the structural core shared by all Cas9 family members. The architectures of Cas9 enzymes define nucleic acid binding clefts, and single-particle electron microscopy reconstructions show that the two structural lobes harboring these clefts undergo guide RNA-induced reorientation to form a central channel where DNA substrates are bound. The observation that extensive structural rearrangements occur before target DNA duplex binding implicates guide RNA loading as a key step in Cas9 activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184034/" 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/PMC4184034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jinek, Martin -- Jiang, Fuguo -- Taylor, David W -- Sternberg, Samuel H -- Kaya, Emine -- Ma, Enbo -- Anders, Carolin -- Hauer, Michael -- Zhou, Kaihong -- Lin, Steven -- Kaplan, Matias -- Iavarone, Anthony T -- Charpentier, Emmanuelle -- Nogales, Eva -- Doudna, Jennifer A -- T32 GM066698/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 14;343(6176):1247997. doi: 10.1126/science.1247997. Epub 2014 Feb 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24505130" target="_blank"〉PubMed〈/a〉
    Keywords: Actinomyces/*enzymology ; Amino Acid Sequence ; Bacterial Proteins/*chemistry ; Caspase 9/*chemistry ; Crystallography, X-Ray ; DNA Cleavage ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/*chemistry ; Streptococcus pyogenes/*enzymology
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  • 51
    Publication Date: 2014-05-17
    Description: Cellular membranes act as signaling platforms and control solute transport. Membrane receptors, transporters, and enzymes communicate with intracellular processes through protein-protein interactions. Using a split-ubiquitin yeast two-hybrid screen that covers a test-space of 6.4 x 10(6) pairs, we identified 12,102 membrane/signaling protein interactions from Arabidopsis. Besides confirmation of expected interactions such as heterotrimeric G protein subunit interactions and aquaporin oligomerization, 〉99% of the interactions were previously unknown. Interactions were confirmed at a rate of 32% in orthogonal in planta split-green flourescent protein interaction assays, which was statistically indistinguishable from the confirmation rate for known interactions collected from literature (38%). Regulatory associations in membrane protein trafficking, turnover, and phosphorylation include regulation of potassium channel activity through abscisic acid signaling, transporter activity by a WNK kinase, and a brassinolide receptor kinase by trafficking-related proteins. These examples underscore the utility of the membrane/signaling protein interaction network for gene discovery and hypothesis generation in plants and other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Alexander M -- Xuan, Yuanhu -- Xu, Meng -- Wang, Rui-Sheng -- Ho, Cheng-Hsun -- Lalonde, Sylvie -- You, Chang Hun -- Sardi, Maria I -- Parsa, Saman A -- Smith-Valle, Erika -- Su, Tianying -- Frazer, Keith A -- Pilot, Guillaume -- Pratelli, Rejane -- Grossmann, Guido -- Acharya, Biswa R -- Hu, Heng-Cheng -- Engineer, Cawas -- Villiers, Florent -- Ju, Chuanli -- Takeda, Kouji -- Su, Zhao -- Dong, Qunfeng -- Assmann, Sarah M -- Chen, Jin -- Kwak, June M -- Schroeder, Julian I -- Albert, Reka -- Rhee, Seung Y -- Frommer, Wolf B -- New York, N.Y. -- Science. 2014 May 16;344(6185):711-6. doi: 10.1126/science.1251358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. ; Department of Physics, Pennsylvania State University, University Park, PA 16802, USA. ; Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. Department of Plant Pathology, Physiology, and Weed Science, Virginia Polytechnic University and State University, Blacksburg, VA 24061, USA. ; Department of Biology, Pennsylvania State University, University Park, PA 16802, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. ; Cell and Developmental Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA. ; Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. Michigan State University-U.S. Department of Energy (MSU-DOE) Plant Research Laboratory and Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. Center for Plant Aging Research, Institute for Basic Science, Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea. ; Department of Plant Biology, Carnegie Institution for Science, CA 94305, USA. wfrommer@stanford.edu srhee@carnegiescience.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833385" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cell Membrane/*metabolism ; Membrane Proteins/genetics/*metabolism ; *Protein Interaction Maps ; Signal Transduction ; Two-Hybrid System Techniques
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  • 52
    Publication Date: 2014-11-02
    Description: Neurotrophins regulate diverse aspects of neuronal development and plasticity, but their precise in vivo functions during neural circuit assembly in the central brain remain unclear. We show that the neurotrophin receptor tropomyosin-related kinase C (TrkC) is required for dendritic growth and branching of mouse cerebellar Purkinje cells. Sparse TrkC knockout reduced dendrite complexity, but global Purkinje cell knockout had no effect. Removal of the TrkC ligand neurotrophin-3 (NT-3) from cerebellar granule cells, which provide major afferent input to developing Purkinje cell dendrites, rescued the dendrite defects caused by sparse TrkC disruption in Purkinje cells. Our data demonstrate that NT-3 from presynaptic neurons (granule cells) is required for TrkC-dependent competitive dendrite morphogenesis in postsynaptic neurons (Purkinje cells)--a previously unknown mechanism of neural circuit development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631524/" 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/PMC4631524/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joo, William -- Hippenmeyer, Simon -- Luo, Liqun -- 5 F31 NS071697/NS/NINDS NIH HHS/ -- F31 NS071697/NS/NINDS NIH HHS/ -- R01 NS050835/NS/NINDS NIH HHS/ -- R01-NS050835/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Oct 31;346(6209):626-9. doi: 10.1126/science.1258996.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. Neurosciences Program, Stanford University, Stanford, CA 94305, USA. ; Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. ; Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. Neurosciences Program, Stanford University, Stanford, CA 94305, USA. lluo@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25359972" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dendrites/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Net/cytology/*growth & development ; *Neurogenesis ; Neurotrophin 3/*metabolism ; Purkinje Cells/*cytology/metabolism ; Receptor, trkC/genetics/*metabolism ; Signal Transduction ; Synapses/physiology
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  • 53
    Publication Date: 2014-11-29
    Description: The capacity of human norovirus (NoV), which causes 〉90% of global epidemic nonbacterial gastroenteritis, to infect a subset of people persistently may contribute to its spread. How such enteric viruses establish persistent infections is not well understood. We found that antibiotics prevented persistent murine norovirus (MNoV) infection, an effect that was reversed by replenishment of the bacterial microbiota. Antibiotics did not prevent tissue infection or affect systemic viral replication but acted specifically in the intestine. The receptor for the antiviral cytokine interferon-lambda, Ifnlr1, as well as the transcription factors Stat1 and Irf3, were required for antibiotics to prevent viral persistence. Thus, the bacterial microbiome fosters enteric viral persistence in a manner counteracted by specific components of the innate immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409937/" 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/PMC4409937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldridge, Megan T -- Nice, Timothy J -- McCune, Broc T -- Yokoyama, Christine C -- Kambal, Amal -- Wheadon, Michael -- Diamond, Michael S -- Ivanova, Yulia -- Artyomov, Maxim -- Virgin, Herbert W -- 1F31CA177194/CA/NCI NIH HHS/ -- 5T32AI007163/AI/NIAID NIH HHS/ -- 5T32CA009547/CA/NCI NIH HHS/ -- F31 CA177194/CA/NCI NIH HHS/ -- R01 AI084887/AI/NIAID NIH HHS/ -- T32 AI007163/AI/NIAID NIH HHS/ -- T32 CA009547/CA/NCI NIH HHS/ -- U19 AI083019/AI/NIAID NIH HHS/ -- U19 AI106772/AI/NIAID NIH HHS/ -- U19 AI109725/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 16;347(6219):266-9. doi: 10.1126/science.1258025. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. virgin@wustl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25431490" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Caliciviridae Infections/drug therapy/immunology/microbiology/*virology ; Cytokines/*physiology ; Female ; Gastroenteritis/drug therapy/immunology/microbiology/*virology ; Intestines/*microbiology/virology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; *Microbiota/drug effects ; Norovirus/immunology/*physiology ; Receptors, Cytokine/genetics/metabolism ; Signal Transduction ; *Symbiosis ; Viral Load ; Virus Replication ; Virus Shedding
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  • 54
    Publication Date: 2014-12-06
    Description: Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naive T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becattini, Simone -- Latorre, Daniela -- Mele, Federico -- Foglierini, Mathilde -- De Gregorio, Corinne -- Cassotta, Antonino -- Fernandez, Blanca -- Kelderman, Sander -- Schumacher, Ton N -- Corti, Davide -- Lanzavecchia, Antonio -- Sallusto, Federica -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):400-6. doi: 10.1126/science.1260668. Epub 2014 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. Institute of Microbiology, ETH Zurich, Zurich, Switzerland. ; Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. ; Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. ; Institute for Research in Biomedicine, Bellinzona, Universita della Svizzera Italiana, Lugano, Switzerland. federica.sallusto@irb.usi.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25477212" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; CD4-Positive T-Lymphocytes/*immunology ; Candida albicans/*immunology ; Cells, Cultured ; Clone Cells ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/*immunology ; Humans ; *Immunologic Memory ; Lymphocyte Activation ; Molecular Sequence Data ; Mycobacterium tuberculosis/*immunology ; Receptors, Antigen, T-Cell/genetics ; T-Lymphocyte Subsets/*immunology ; Th1 Cells/immunology ; Th17 Cells/immunology ; Th2 Cells/immunology ; Vaccines/*immunology
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  • 55
    Publication Date: 2014-12-17
    Description: The emergence of artemisinin resistance in Southeast Asia imperils efforts to reduce the global malaria burden. We genetically modified the Plasmodium falciparum K13 locus using zinc-finger nucleases and measured ring-stage survival rates after drug exposure in vitro; these rates correlate with parasite clearance half-lives in artemisinin-treated patients. With isolates from Cambodia, where resistance first emerged, survival rates decreased from 13 to 49% to 0.3 to 2.4% after the removal of K13 mutations. Conversely, survival rates in wild-type parasites increased from 〈/=0.6% to 2 to 29% after the insertion of K13 mutations. These mutations conferred elevated resistance to recent Cambodian isolates compared with that of reference lines, suggesting a contemporary contribution of additional genetic factors. Our data provide a conclusive rationale for worldwide K13-propeller sequencing to identify and eliminate artemisinin-resistant parasites.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349400/" 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/PMC4349400/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Straimer, Judith -- Gnadig, Nina F -- Witkowski, Benoit -- Amaratunga, Chanaki -- Duru, Valentine -- Ramadani, Arba Pramundita -- Dacheux, Melanie -- Khim, Nimol -- Zhang, Lei -- Lam, Stephen -- Gregory, Philip D -- Urnov, Fyodor D -- Mercereau-Puijalon, Odile -- Benoit-Vical, Francoise -- Fairhurst, Rick M -- Menard, Didier -- Fidock, David A -- R01 AI109023/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):428-31. doi: 10.1126/science.1260867. Epub 2014 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA. ; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie de Coordination UPR8241, Toulouse, France. Universite de Toulouse, UPS, Institut National Polytechnique de Toulouse, Toulouse, France. ; Sangamo BioSciences, Richmond, CA, USA. ; Institut Pasteur, Parasite Molecular Immunology Unit, Paris, France. ; Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA. Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. df2260@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25502314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antimalarials/*pharmacology ; Artemisinins/*pharmacology ; Cambodia ; Drug Resistance/*genetics ; Genetic Loci ; Humans ; Malaria, Falciparum/drug therapy/parasitology ; Molecular Sequence Data ; Mutation ; Plasmodium falciparum/*drug effects/*genetics ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/*genetics
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  • 56
    Publication Date: 2013-11-23
    Description: Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for 〉99% of schistosomiasis cases worldwide.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136436/" 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/PMC4136436/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Valentim, Claudia L L -- Cioli, Donato -- Chevalier, Frederic D -- Cao, Xiaohang -- Taylor, Alexander B -- Holloway, Stephen P -- Pica-Mattoccia, Livia -- Guidi, Alessandra -- Basso, Annalisa -- Tsai, Isheng J -- Berriman, Matthew -- Carvalho-Queiroz, Claudia -- Almeida, Marcio -- Aguilar, Hector -- Frantz, Doug E -- Hart, P John -- LoVerde, Philip T -- Anderson, Timothy J C -- 098051/Wellcome Trust/United Kingdom -- 5R21-AI072704/AI/NIAID NIH HHS/ -- 5R21-AI096277/AI/NIAID NIH HHS/ -- C06 RR013556/RR/NCRR NIH HHS/ -- HHSN272201000005I/PHS HHS/ -- R01 AI097576/AI/NIAID NIH HHS/ -- R01-AI097576/AI/NIAID NIH HHS/ -- R21 AI072704/AI/NIAID NIH HHS/ -- R21 AI096277/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1385-9. doi: 10.1126/science.1243106. Epub 2013 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biochemistry and Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24263136" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Drug Resistance/*genetics ; Gene Knockdown Techniques ; Genetic Linkage ; Helminth Proteins/*genetics ; Humans ; Molecular Sequence Data ; Mutation ; Oxamniquine/*pharmacology ; Phylogeny ; Protein Conformation ; Quantitative Trait Loci ; RNA Interference ; Schistosoma mansoni/*drug effects/*genetics ; Schistosomicides/*pharmacology ; Sulfotransferases/chemistry/classification/*genetics
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  • 57
    Publication Date: 2013-06-08
    Description: Evolutionarily young genes that serve essential functions represent a paradox; they must perform a function that either was not required until after their birth or was redundant with another gene. How young genes rapidly acquire essential function is largely unknown. We traced the evolutionary steps by which the Drosophila gene Umbrea acquired an essential role in chromosome segregation in D. melanogaster since the gene's origin less than 15 million years ago. Umbrea neofunctionalization occurred via loss of an ancestral heterochromatin-localizing domain, followed by alterations that rewired its protein interaction network and led to species-specific centromere localization. Our evolutionary cell biology approach provides temporal and mechanistic detail about how young genes gain essential function. Such innovations may constantly alter the repertoire of centromeric proteins in eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119826/" 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/PMC4119826/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ross, Benjamin D -- Rosin, Leah -- Thomae, Andreas W -- Hiatt, Mary Alice -- Vermaak, Danielle -- de la Cruz, Aida Flor A -- Imhof, Axel -- Mellone, Barbara G -- Malik, Harmit S -- R01 GM074108/GM/NIGMS NIH HHS/ -- R01GM074108/GM/NIGMS NIH HHS/ -- T32HG000035/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1211-4. doi: 10.1126/science.1234393.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744945" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Centromere/genetics/*physiology ; Chromosomal Proteins, Non-Histone/*genetics ; Drosophila/*genetics ; Drosophila Proteins/*genetics ; *Evolution, Molecular ; Gene Duplication ; Genes, Insect/*physiology ; Molecular Sequence Data
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  • 58
    Publication Date: 2013-08-31
    Description: Invasion of microbial DNA into the cytoplasm of animal cells triggers a cascade of host immune reactions that help clear the infection; however, self DNA in the cytoplasm can cause autoimmune diseases. Biochemical approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas(-/-)) mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. cGas(-/-) mice were more susceptible to lethal infection with herpes simplex virus 1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863637/" 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/PMC3863637/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Xiao-Dong -- Wu, Jiaxi -- Gao, Daxing -- Wang, Hua -- Sun, Lijun -- Chen, Zhijian J -- 5T32AI070116/AI/NIAID NIH HHS/ -- AI-093967/AI/NIAID NIH HHS/ -- R01 AI093967/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1390-4. doi: 10.1126/science.1244040. Epub 2013 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23989956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/biosynthesis ; DNA, Viral/genetics/immunology ; Dendritic Cells/immunology ; Fibroblasts/immunology ; Herpes Simplex/*immunology ; *Herpesvirus 1, Human ; Interferon Regulatory Factor-3/genetics ; Interferon-beta/*biosynthesis/genetics ; Lymphocyte Activation ; Macrophages/immunology ; Mice ; Mice, Knockout ; Nucleotidyltransferases/genetics/*immunology ; Signal Transduction ; T-Lymphocytes/immunology ; Transfection
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  • 59
    Publication Date: 2013-07-28
    Description: The essential bacterial protein FtsZ is a guanosine triphosphatase that self-assembles into a structure at the division site termed the "Z ring". During cytokinesis, the Z ring exerts a constrictive force on the membrane by using the chemical energy of guanosine triphosphate hydrolysis. However, the structural basis of this constriction remains unresolved. Here, we present the crystal structure of a guanosine diphosphate-bound Mycobacterium tuberculosis FtsZ protofilament, which exhibits a curved conformational state. The structure reveals a longitudinal interface that is important for function. The protofilament curvature highlights a hydrolysis-dependent conformational switch at the T3 loop that leads to longitudinal bending between subunits, which could generate sufficient force to drive cytokinesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816583/" 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/PMC3816583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ying -- Hsin, Jen -- Zhao, Lingyun -- Cheng, Yiwen -- Shang, Weina -- Huang, Kerwyn Casey -- Wang, Hong-Wei -- Ye, Sheng -- 1F32GM100677-01A1/GM/NIGMS NIH HHS/ -- DP2 OD006466/OD/NIH HHS/ -- DP2OD006466/OD/NIH HHS/ -- F32 GM100677/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):392-5. doi: 10.1126/science.1239248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Institute, Zhejiang University, Hangzhou, 310058 Zhejiang, P.R. China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888039" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Cell Membrane/physiology ; Crystallography, X-Ray ; *Cytokinesis ; Cytoskeletal Proteins/*chemistry/genetics/*metabolism ; Escherichia coli/chemistry ; Guanosine Diphosphate/chemistry/metabolism ; Guanosine Triphosphate/metabolism ; Hydrolysis ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Mycobacterium tuberculosis/*chemistry/physiology ; Point Mutation ; Protein Conformation ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Staphylococcus aureus/chemistry
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  • 60
    Publication Date: 2013-10-26
    Description: Painful venoms are used to deter predators. Pain itself, however, can signal damage and thus serves an important adaptive function. Evolution to reduce general pain responses, although valuable for preying on venomous species, is rare, likely because it comes with the risk of reduced response to tissue damage. Bark scorpions capitalize on the protective pain pathway of predators by inflicting intensely painful stings. However, grasshopper mice regularly attack and consume bark scorpions, grooming only briefly when stung. Bark scorpion venom induces pain in many mammals (house mice, rats, humans) by activating the voltage-gated Na(+) channel Nav1.7, but has no effect on Nav1.8. Grasshopper mice Nav1.8 has amino acid variants that bind bark scorpion toxins and inhibit Na(+) currents, blocking action potential propagation and inducing analgesia. Thus, grasshopper mice have solved the predator-pain problem by using a toxin bound to a nontarget channel to block transmission of the pain signals the venom itself is initiating.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172297/" 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/PMC4172297/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rowe, Ashlee H -- Xiao, Yucheng -- Rowe, Matthew P -- Cummins, Theodore R -- Zakon, Harold H -- NS 053422/NS/NINDS NIH HHS/ -- R01 NS053422/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 25;342(6157):441-6. doi: 10.1126/science.1236451.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Neurobiology, The University of Texas at Austin, Austin, TX 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24159039" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects/physiology ; Amino Acid Sequence ; Animals ; Arvicolinae/*metabolism ; *Food Chain ; Formaldehyde/pharmacology ; Mice ; Molecular Sequence Data ; NAV1.7 Voltage-Gated Sodium Channel/chemistry/genetics/*metabolism ; NAV1.8 Voltage-Gated Sodium Channel/chemistry/genetics/*metabolism ; Pain/chemically induced/*metabolism ; *Predatory Behavior ; Protein Structure, Tertiary ; Scorpion Venoms
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  • 61
    Publication Date: 2013-03-23
    Description: Glycosylated alpha-dystroglycan (alpha-DG) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary Walker-Warburg syndrome (WWS). At least eight proteins are critical to glycosylate alpha-DG, but many genes mutated in WWS remain unknown. To identify modifiers of alpha-DG, we performed a haploid screen for Lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated alpha-DG to enter cells. In complementary screens, we profiled cells for absence of alpha-DG carbohydrate chains or biochemically related glycans. This revealed virus host factors and a suite of glycosylation units, including all known Walker-Warburg genes and five additional factors critical for the modification of alpha-DG. Our findings accentuate the complexity of this posttranslational feature and point out genes defective in dystroglycanopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919138/" 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/PMC3919138/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jae, Lucas T -- Raaben, Matthijs -- Riemersma, Moniek -- van Beusekom, Ellen -- Blomen, Vincent A -- Velds, Arno -- Kerkhoven, Ron M -- Carette, Jan E -- Topaloglu, Haluk -- Meinecke, Peter -- Wessels, Marja W -- Lefeber, Dirk J -- Whelan, Sean P -- van Bokhoven, Hans -- Brummelkamp, Thijn R -- AI057159/AI/NIAID NIH HHS/ -- AI081842/AI/NIAID NIH HHS/ -- R01 AI081842/AI/NIAID NIH HHS/ -- U54 AI057159/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 26;340(6131):479-83. doi: 10.1126/science.1233675. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519211" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Dystroglycans/*metabolism ; Female ; Glycosylation ; Haploidy ; Host-Pathogen Interactions/*genetics ; Humans ; Infant ; Lassa Fever/*genetics/virology ; Lassa virus/*physiology ; Male ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Mutation ; Pedigree ; Proteome/*metabolism ; *Virus Internalization ; Walker-Warburg Syndrome/*genetics
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  • 62
    Publication Date: 2013-11-10
    Description: Environmental and hormonal signals cause reorganization of microtubule arrays in higher plants, but the mechanisms driving these transitions have remained elusive. The organization of these arrays is required to direct morphogenesis. We discovered that microtubule severing by the protein katanin plays a crucial and unexpected role in the reorientation of cortical arrays, as triggered by blue light. Imaging and genetic experiments revealed that phototropin photoreceptors stimulate katanin-mediated severing specifically at microtubule intersections, leading to the generation of new microtubules at these locations. We show how this activity serves as the basis for a mechanism that amplifies microtubules orthogonal to the initial array, thereby driving array reorientation. Our observations show how severing is used constructively to build a new microtubule array.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindeboom, Jelmer J -- Nakamura, Masayoshi -- Hibbel, Anneke -- Shundyak, Kostya -- Gutierrez, Ryan -- Ketelaar, Tijs -- Emons, Anne Mie C -- Mulder, Bela M -- Kirik, Viktor -- Ehrhardt, David W -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1245533. doi: 10.1126/science.1245533. Epub 2013 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24200811" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/genetics/*metabolism ; Arabidopsis/genetics/growth & development/*metabolism/*ultrastructure ; Arabidopsis Proteins/genetics/*metabolism ; Hypocotyl/metabolism/ultrastructure ; Light ; Microtubules/*metabolism/ultrastructure ; Phosphoproteins/metabolism ; *Phototropism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction
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  • 63
    Publication Date: 2013-07-03
    Description: Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is a devastating disease that can cause severe yield losses. A previously uncharacterized Pgt race, designated Ug99, has overcome most of the widely used resistance genes and is threatening major wheat production areas. Here, we demonstrate that the Sr35 gene from Triticum monococcum is a coiled-coil, nucleotide-binding, leucine-rich repeat gene that confers near immunity to Ug99 and related races. This gene is absent in the A-genome diploid donor and in polyploid wheat but is effective when transferred from T. monococcum to polyploid wheat. The cloning of Sr35 opens the door to the use of biotechnological approaches to control this devastating disease and to analyses of the molecular interactions that define the wheat-rust pathosystem.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748951/" 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/PMC4748951/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saintenac, Cyrille -- Zhang, Wenjun -- Salcedo, Andres -- Rouse, Matthew N -- Trick, Harold N -- Akhunov, Eduard -- Dubcovsky, Jorge -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):783-6. doi: 10.1126/science.1239022. Epub 2013 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, Kansas State University, Manhattan, KS 66506, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23811222" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; *Basidiomycota/pathogenicity ; Cloning, Molecular ; Disease Resistance/genetics ; *Genes, Plant ; Haplotypes ; Molecular Sequence Annotation ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Diseases/genetics/*immunology/microbiology ; Plant Proteins/chemistry/genetics ; Plant Stems/microbiology ; Plants, Genetically Modified ; Polymorphism, Single Nucleotide ; Polyploidy ; Sequence Analysis, DNA ; Triticum/*genetics/immunology/microbiology
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  • 64
    Publication Date: 2013-04-06
    Description: A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784322/" 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/PMC3784322/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Apps, Richard -- Qi, Ying -- Carlson, Jonathan M -- Chen, Haoyan -- Gao, Xiaojiang -- Thomas, Rasmi -- Yuki, Yuko -- Del Prete, Greg Q -- Goulder, Philip -- Brumme, Zabrina L -- Brumme, Chanson J -- John, Mina -- Mallal, Simon -- Nelson, George -- Bosch, Ronald -- Heckerman, David -- Stein, Judy L -- Soderberg, Kelly A -- Moody, M Anthony -- Denny, Thomas N -- Zeng, Xue -- Fang, Jingyuan -- Moffett, Ashley -- Lifson, Jeffrey D -- Goedert, James J -- Buchbinder, Susan -- Kirk, Gregory D -- Fellay, Jacques -- McLaren, Paul -- Deeks, Steven G -- Pereyra, Florencia -- Walker, Bruce -- Michael, Nelson L -- Weintrob, Amy -- Wolinsky, Steven -- Liao, Wilson -- Carrington, Mary -- 5-M01-RR-00722/RR/NCRR NIH HHS/ -- HHSN261200800001E/CA/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- K08 AR057763/AR/NIAMS NIH HHS/ -- K08AR057763/AR/NIAMS NIH HHS/ -- K24 AI069994/AI/NIAID NIH HHS/ -- K24AI069994/AI/NIAID NIH HHS/ -- N02-CP-55504/CP/NCI NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-24/AI/NIAID NIH HHS/ -- P30 MH62246/MH/NIMH NIH HHS/ -- PG/09/077/27964/British Heart Foundation/United Kingdom -- R01 AI046995/AI/NIAID NIH HHS/ -- R01 AI060460/AI/NIAID NIH HHS/ -- R01 AI087145/AI/NIAID NIH HHS/ -- R01 AR065174/AR/NIAMS NIH HHS/ -- R01-AI046995/AI/NIAID NIH HHS/ -- R01-AI060460/AI/NIAID NIH HHS/ -- R01-DA-04334/DA/NIDA NIH HHS/ -- R01-DA-12568/DA/NIDA NIH HHS/ -- R01-DA04334/DA/NIDA NIH HHS/ -- R01-DA12568/DA/NIDA NIH HHS/ -- R24 AI067039/AI/NIAID NIH HHS/ -- U01-AI-067854/AI/NIAID NIH HHS/ -- U01-AI-35039/AI/NIAID NIH HHS/ -- U01-AI-35040/AI/NIAID NIH HHS/ -- U01-AI-35041/AI/NIAID NIH HHS/ -- U01-AI-35042/AI/NIAID NIH HHS/ -- U01-AI-35043/AI/NIAID NIH HHS/ -- U01-AI-37613/AI/NIAID NIH HHS/ -- U01-AI-37984/AI/NIAID NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):87-91. doi: 10.1126/science.1232685.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer and Inflammation Program, Laboratory of Experimental Immunology, Science Applications International Corporation-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23559252" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/genetics ; Alleles ; Amino Acid Sequence ; Anti-Retroviral Agents/therapeutic use ; Crohn Disease/genetics/immunology ; *Gene Expression Regulation ; HIV/genetics/*immunology ; HIV Infections/drug therapy/*genetics/*immunology ; HLA-C Antigens/*genetics ; Humans ; Immunodominant Epitopes/genetics ; Molecular Sequence Data ; Mutation ; Peptide Fragments/immunology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Load/genetics
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  • 65
    Publication Date: 2013-02-02
    Description: The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778192/" 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/PMC3778192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shapiro, Michael D -- Kronenberg, Zev -- Li, Cai -- Domyan, Eric T -- Pan, Hailin -- Campbell, Michael -- Tan, Hao -- Huff, Chad D -- Hu, Haofu -- Vickrey, Anna I -- Nielsen, Sandra C A -- Stringham, Sydney A -- Hu, Hao -- Willerslev, Eske -- Gilbert, M Thomas P -- Yandell, Mark -- Zhang, Guojie -- Wang, Jun -- GO RC2HG005619/HG/NHGRI NIH HHS/ -- R01 GM104390/GM/NIGMS NIH HHS/ -- R01 HG004694/HG/NHGRI NIH HHS/ -- R01HG004694/HG/NHGRI NIH HHS/ -- R44 HG006579/HG/NHGRI NIH HHS/ -- RC2 HG005619/HG/NHGRI NIH HHS/ -- T32 GM007464/GM/NIGMS NIH HHS/ -- T32 HD007491/HD/NICHD NIH HHS/ -- T32GM007464/GM/NIGMS NIH HHS/ -- T32HD07491/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1063-7. doi: 10.1126/science.1230422. Epub 2013 Jan 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. mike.shapiro@utah.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23371554" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Domestic/anatomy & histology/classification/genetics ; Animals, Wild/anatomy & histology/classification/genetics ; Breeding ; Columbidae/anatomy & histology/*classification/*genetics ; *Evolution, Molecular ; Feathers/anatomy & histology ; *Genetic Variation ; Genome ; Head/*anatomy & histology ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; Receptor, EphB2/genetics ; Sequence Analysis, DNA
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  • 66
    Publication Date: 2013-04-27
    Description: Senescent and damaged mitochondria undergo selective mitophagic elimination through mechanisms requiring two Parkinson's disease factors, the mitochondrial kinase PINK1 (PTEN-induced putative kinase protein 1; PTEN is phosphatase and tensin homolog) and the cytosolic ubiquitin ligase Parkin. The nature of the PINK-Parkin interaction and the identity of key factors directing Parkin to damaged mitochondria are unknown. We show that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. Ablation of Mfn2 in mouse cardiac myocytes prevented depolarization-induced translocation of Parkin to the mitochondria and suppressed mitophagy. Accumulation of morphologically and functionally abnormal mitochondria induced respiratory dysfunction in Mfn2-deficient mouse embryonic fibroblasts and cardiomyocytes and in Parkin-deficient Drosophila heart tubes, causing dilated cardiomyopathy. Thus, Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774525/" 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/PMC3774525/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Yun -- Dorn, Gerald W 2nd -- R01 HL059888/HL/NHLBI NIH HHS/ -- R21 HL107276/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 26;340(6131):471-5. doi: 10.1126/science.1231031.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23620051" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Autophagy ; Cardiomyopathies/enzymology ; Drosophila melanogaster ; Fibroblasts/ultrastructure ; GTP Phosphohydrolases/genetics/*metabolism ; HEK293 Cells ; Humans ; Mice ; Mice, Mutant Strains ; Mitochondria/enzymology ; Mitochondria, Heart/*enzymology ; Molecular Sequence Data ; Myocytes, Cardiac/*enzymology/ultrastructure ; Phosphorylation ; Protein Kinases/*metabolism ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination
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  • 67
    Publication Date: 2013-10-05
    Description: Most models of gene duplication assume that the ancestral functions of the preduplication gene are independent and can therefore be neatly partitioned between descendant paralogs. However, many gene products, such as transcriptional regulators, are components within cooperative assemblies; here, we show that a natural consequence of duplication and divergence of such proteins can be competitive interference between the paralogs. Our example is based on the duplication of the essential MADS-box transcriptional regulator Mcm1, which is found in all fungi and regulates a large set of genes. We show that a set of historical amino acid sequence substitutions minimized paralog interference in contemporary species and, in doing so, increased the molecular complexity of this gene regulatory network. We propose that paralog interference is a common constraint on gene duplicate evolution, and its resolution, which can generate additional regulatory complexity, is needed to stabilize duplicated genes in the genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911913/" 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/PMC3911913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, Christopher R -- Hanson-Smith, Victor -- Johnson, Alexander D -- F32 GM108299/GM/NIGMS NIH HHS/ -- R01 GM037049/GM/NIGMS NIH HHS/ -- R01 GM057049/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 4;342(6154):104-8. doi: 10.1126/science.1240810.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbiology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24092741" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arginine/genetics ; Candida albicans/genetics ; *Evolution, Molecular ; *Gene Duplication ; *Gene Regulatory Networks ; Kluyveromyces/genetics ; Minichromosome Maintenance 1 Protein/*genetics ; Molecular Sequence Data ; Saccharomyces cerevisiae/genetics ; Sequence Deletion ; *Transcription, Genetic
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  • 68
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-23
    Description: In many mammalian tissues, mature differentiated cells are replaced by self-renewing stem cells, either continuously during homeostasis or in response to challenge and injury. For example, hematopoietic stem cells generate all mature blood cells, including monocytes, which have long been thought to be the major source of tissue macrophages. Recently, however, major macrophage populations were found to be derived from embryonic progenitors and to renew independently of hematopoietic stem cells. This process may not require progenitors, as mature macrophages can proliferate in response to specific stimuli indefinitely and without transformation or loss of functional differentiation. These findings suggest that macrophages are mature differentiated cells that may have a self-renewal potential similar to that of stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sieweke, Michael H -- Allen, Judith E -- MR/J001929/1/Medical Research Council/United Kingdom -- MR/K01207X1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):1242974. doi: 10.1126/science.1242974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Universite, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24264994" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Proliferation ; Cytokines/metabolism ; Embryonic Stem Cells/cytology ; Humans ; Macrophages/*cytology ; Mice ; Monocytes/cytology ; Rats ; Signal Transduction ; Stem Cells/*cytology
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  • 69
    Publication Date: 2013-10-05
    Description: Mitochondrial morphology is crucial for tissue homeostasis, but its role in cell differentiation is unclear. We found that mitochondrial fusion was required for proper cardiomyocyte development. Ablation of mitochondrial fusion proteins Mitofusin 1 and 2 in the embryonic mouse heart, or gene-trapping of Mitofusin 2 or Optic atrophy 1 in mouse embryonic stem cells (ESCs), arrested mouse heart development and impaired differentiation of ESCs into cardiomyocytes. Gene expression profiling revealed decreased levels of transcription factors transforming growth factor-beta/bone morphogenetic protein, serum response factor, GATA4, and myocyte enhancer factor 2, linked to increased Ca(2+)-dependent calcineurin activity and Notch1 signaling that impaired ESC differentiation. Orchestration of cardiomyocyte differentiation by mitochondrial morphology reveals how mitochondria, Ca(2+), and calcineurin interact to regulate Notch1 signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasahara, Atsuko -- Cipolat, Sara -- Chen, Yun -- Dorn, Gerald W 2nd -- Scorrano, Luca -- GPP10005/Telethon/Italy -- R01 HL059888/HL/NHLBI NIH HHS/ -- R01 HL59888/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):734-7. doi: 10.1126/science.1241359. Epub 2013 Oct 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Physiology and Metabolism, University of Geneva, 1206 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24091702" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcineurin/*metabolism ; Calcineurin Inhibitors ; Cell Differentiation/genetics/*physiology ; GTP Phosphohydrolases/genetics/metabolism ; Gene Expression Profiling ; Heart/embryology ; Mice ; Mice, Knockout ; Mitochondrial Dynamics/genetics/*physiology ; Myocytes, Cardiac/*cytology/ultrastructure ; Receptor, Notch1/*metabolism ; Signal Transduction ; Transcription Factors/genetics/metabolism
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  • 70
    Publication Date: 2013-03-23
    Description: Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/" 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/PMC3644373/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Chong -- Jiang, Yi -- Ma, Jinming -- Wu, Huixian -- Wacker, Daniel -- Katritch, Vsevolod -- Han, Gye Won -- Liu, Wei -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Gao, Xiang -- Zhou, X Edward -- Melcher, Karsten -- Zhang, Chenghai -- Bai, Fang -- Yang, Huaiyu -- Yang, Linlin -- Jiang, Hualiang -- Roth, Bryan L -- Cherezov, Vadim -- Stevens, Raymond C -- Xu, H Eric -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DA027170/DA/NIDA NIH HHS/ -- R01 DA27170/DA/NIDA NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH61887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH82441/MH/NIMH NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 May 3;340(6132):610-4. doi: 10.1126/science.1232807. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519210" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Dihydroergotamine/chemistry/*metabolism ; Ergotamine/chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lysergic Acid Diethylamide/chemistry/metabolism ; Models, Molecular ; Molecular Docking Simulation ; Molecular Sequence Data ; Mutagenesis ; Norfenfluramine/chemistry/metabolism ; Pindolol/analogs & derivatives/chemistry/metabolism ; Propranolol/chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptor, Serotonin, 5-HT1B/*chemistry/genetics/*metabolism ; Serotonin 5-HT1 Receptor Agonists/*chemistry/*metabolism ; Tryptamines/chemistry/metabolism
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  • 71
    Publication Date: 2013-08-24
    Description: Small open reading frames (smORFs) are short DNA sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies. Such conservation suggests that the mechanisms for heart regulation are ancient and that smORFs may be a fundamental genome component that should be studied systematically.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Magny, Emile G -- Pueyo, Jose Ignacio -- Pearl, Frances M G -- Cespedes, Miguel Angel -- Niven, Jeremy E -- Bishop, Sarah A -- Couso, Juan Pablo -- 087516/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 Sep 6;341(6150):1116-20. doi: 10.1126/science.1238802. Epub 2013 Aug 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23970561" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/*metabolism ; Conserved Sequence ; Drosophila Proteins/chemistry/genetics/metabolism/*physiology ; Drosophila melanogaster ; Evolution, Molecular ; Ion Transport ; Molecular Sequence Data ; Muscle Proteins/chemistry/genetics/*physiology ; Muscle, Skeletal/*metabolism ; *Myocardial Contraction ; Myocardium/*metabolism ; Open Reading Frames ; Peptides/chemistry/genetics/*physiology ; Protein Structure, Secondary ; Transaldolase/genetics/metabolism
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  • 72
    Publication Date: 2013-06-01
    Description: Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763809/" 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/PMC3763809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kato, Hidenori -- Jiang, Jiansheng -- Zhou, Bing-Rui -- Rozendaal, Marieke -- Feng, Hanqiao -- Ghirlando, Rodolfo -- Xiao, T Sam -- Straight, Aaron F -- Bai, Yawen -- R01 GM074728/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- ZIA AI000960-07/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 31;340(6136):1110-3. doi: 10.1126/science.1235532.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723239" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Autoantigens/metabolism ; Binding Sites ; Centromere/*metabolism ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; Conserved Sequence ; Drosophila ; Histones/*metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Molecular Sequence Data ; Nucleosomes/*metabolism ; Protein Structure, Secondary
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  • 73
    Publication Date: 2013-12-18
    Description: Erythropoietin is a signaling glycoprotein that controls the fundamental process of erythropoiesis, orchestrating the production and maintenance of red blood cells. As administrated clinically, erythropoietin has a polypeptide backbone with complex dishomogeneity in its carbohydrate domains. Here we describe the total synthesis of homogeneous erythropoietin with consensus carbohydrate domains incorporated at all of the native glycosylation sites. The oligosaccharide sectors were built by total synthesis and attached stereospecifically to peptidyl fragments of the wild-type primary sequence, themselves obtained by solid-phase peptide synthesis. The glycopeptidyl constructs were joined by chemical ligation, followed by metal-free dethiylation, and subsequently folded. This homogeneous erythropoietin glycosylated at the three wild-type aspartates with N-linked high-mannose sialic acid-containing oligosaccharides and O-linked glycophorin exhibits Procrit-level in vivo activity in mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080428/" 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/PMC4080428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Ping -- Dong, Suwei -- Shieh, Jae-Hung -- Peguero, Elizabeth -- Hendrickson, Ronald -- Moore, Malcolm A S -- Danishefsky, Samuel J -- HL025848/HL/NHLBI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 GM109760/GM/NIGMS NIH HHS/ -- R01 HL025848/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1357-60. doi: 10.1126/science.1245095.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24337294" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Aspartic Acid/chemistry ; Cells, Cultured ; Consensus Sequence ; Dose-Response Relationship, Drug ; Erythrocyte Count ; Erythropoietin/*administration & dosage/*chemical synthesis/chemistry ; Glycophorin/chemistry ; Glycosylation ; Injections, Subcutaneous ; Mannose/chemistry ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; N-Acetylneuraminic Acid/chemistry ; Oligosaccharides/chemistry ; Reticulocytes/drug effects
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  • 74
    Publication Date: 2013-01-26
    Description: The human genome contains ~50 genes that were derived from transposable elements or transposons, and many are now integral components of cellular gene expression programs. The human THAP9 gene is related to the Drosophila P-element transposase. Here, we show that human THAP9 can mobilize Drosophila P-elements in both Drosophila and human cells. Chimeric proteins formed between the Drosophila P-element transposase N-terminal THAP DNA binding domain and the C-terminal regions of human THAP9 can also mobilize Drosophila P elements. Our results indicate that human THAP9 is an active DNA transposase that, although "domesticated," still retains the catalytic activity to mobilize P transposable elements across species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779457/" 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/PMC3779457/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Majumdar, Sharmistha -- Singh, Anita -- Rio, Donald C -- R01 GM048862/GM/NIGMS NIH HHS/ -- R01 GM094890/GM/NIGMS NIH HHS/ -- R01 GM097352/GM/NIGMS NIH HHS/ -- R01 GM104385/GM/NIGMS NIH HHS/ -- R01GM094890/GM/NIGMS NIH HHS/ -- R01GM104385/GM/NIGMS NIH HHS/ -- R01GM48862/GM/NIGMS NIH HHS/ -- R01GM61987/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):446-8. doi: 10.1126/science.1231789.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349291" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; *DNA Transposable Elements ; Drosophila/genetics ; Genome, Human ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Recombinant Fusion Proteins/metabolism ; Sequence Analysis, DNA ; Transfection ; Transposases/chemistry/*genetics/*metabolism
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  • 75
    Publication Date: 2013-07-03
    Description: Wheat stem rust, caused by the fungus Puccinia graminis f. sp. tritici, afflicts bread wheat (Triticum aestivum). New virulent races collectively referred to as "Ug99" have emerged, which threaten global wheat production. The wheat gene Sr33, introgressed from the wild relative Aegilops tauschii into bread wheat, confers resistance to diverse stem rust races, including the Ug99 race group. We cloned Sr33, which encodes a coiled-coil, nucleotide-binding, leucine-rich repeat protein. Sr33 is orthologous to the barley (Hordeum vulgare) Mla mildew resistance genes that confer resistance to Blumeria graminis f. sp. hordei. The wheat Sr33 gene functions independently of RAR1, SGT1, and HSP90 chaperones. Haplotype analysis from diverse collections of Ae. tauschii placed the origin of Sr33 resistance near the southern coast of the Caspian Sea.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Periyannan, Sambasivam -- Moore, John -- Ayliffe, Michael -- Bansal, Urmil -- Wang, Xiaojing -- Huang, Li -- Deal, Karin -- Luo, Mingcheng -- Kong, Xiuying -- Bariana, Harbans -- Mago, Rohit -- McIntosh, Robert -- Dodds, Peter -- Dvorak, Jan -- Lagudah, Evans -- New York, N.Y. -- Science. 2013 Aug 16;341(6147):786-8. doi: 10.1126/science.1239028. Epub 2013 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Commonwealth Scientific and Industrial Research Organization (CSIRO) Plant Industry, Canberra, ACT 2601, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23811228" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Basidiomycota/pathogenicity ; Cloning, Molecular ; Disease Resistance/genetics ; *Genes, Plant ; Haplotypes ; Hordeum/genetics ; Hybridization, Genetic ; Molecular Chaperones/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Plant Diseases/genetics/*immunology/microbiology ; Plant Proteins/chemistry/genetics/metabolism ; Plant Stems/microbiology ; Plants, Genetically Modified ; Poaceae/*genetics ; Synteny ; Triticum/*genetics/*microbiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 76
    Publication Date: 2013-03-23
    Description: Kinesin-mediated cargo transport is required for many cellular functions and plays a key role in pathological processes. Structural information on how kinesins recognize their cargoes is required for a molecular understanding of this fundamental and ubiquitous process. Here, we present the crystal structure of the tetratricopeptide repeat domain of kinesin light chain 2 in complex with a cargo peptide harboring a "tryptophan-acidic" motif derived from SKIP (SifA-kinesin interacting protein), a critical host determinant in Salmonella pathogenesis and a regulator of lysosomal positioning. Structural data together with biophysical, biochemical, and cellular assays allow us to propose a framework for intracellular transport based on the binding by kinesin-1 of W-acidic cargo motifs through a combination of electrostatic interactions and sequence-specific elements, providing direct molecular evidence of the mechanisms for kinesin-1:cargo recognition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693442/" 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/PMC3693442/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pernigo, Stefano -- Lamprecht, Anneri -- Steiner, Roberto A -- Dodding, Mark P -- 097316/Wellcome Trust/United Kingdom -- British Heart Foundation/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Apr 19;340(6130):356-9. doi: 10.1126/science.1234264. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519214" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Bacterial Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Glycoproteins/*chemistry/metabolism ; HeLa Cells ; Humans ; Mice ; Microtubule-Associated Proteins/*chemistry/genetics/metabolism ; Molecular Sequence Data ; Mutation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Tryptophan/chemistry/genetics/metabolism
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  • 77
    Publication Date: 2013-12-07
    Description: The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike alpha2-6-linked receptors and strong preference for a subset of avian-like alpha2-3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954636/" 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/PMC3954636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Rui -- de Vries, Robert P -- Zhu, Xueyong -- Nycholat, Corwin M -- McBride, Ryan -- Yu, Wenli -- Paulson, James C -- Wilson, Ian A -- GM62116/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R56 AI099275/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1230-5. doi: 10.1126/science.1243761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311689" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Birds ; Carbohydrate Conformation ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*metabolism ; Humans ; Influenza A Virus, H7N9 Subtype/*metabolism/*pathogenicity ; Influenza in Birds/transmission/virology ; Influenza, Human/transmission/virology ; Ligands ; Microarray Analysis ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Polysaccharides/chemistry/*metabolism ; Receptors, Virus/chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism
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  • 78
    Publication Date: 2013-06-08
    Description: Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730555/" 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/PMC4730555/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, Christian H -- Healey, Eleanor -- van Erp, Susan -- Bishop, Benjamin -- Tang, Chenxiang -- Gilbert, Robert J C -- Aricescu, A Radu -- Pasterkamp, R Jeroen -- Siebold, Christian -- 082301/Wellcome Trust/United Kingdom -- 083111/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 097301/Wellcome Trust/United Kingdom -- A14414/Cancer Research UK/United Kingdom -- G0700232/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Jul 5;341(6141):77-80. doi: 10.1126/science.1232322. Epub 2013 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. christian@strubi.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744777" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biophysical Phenomena ; Cell Adhesion Molecules, Neuronal/*chemistry/genetics ; Conserved Sequence ; Crystallography, X-Ray ; Humans ; Membrane Proteins/*chemistry ; Mutation ; Oligopeptides/chemistry ; Protein Structure, Tertiary ; Signal Transduction
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  • 79
    Publication Date: 2013-06-08
    Description: Phosphatase and tensin homolog on chromosome ten (PTEN) is a tumor suppressor and an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified a 576-amino acid translational variant of PTEN, termed PTEN-Long, that arises from an alternative translation start site 519 base pairs upstream of the ATG initiation sequence, adding 173 N-terminal amino acids to the normal PTEN open reading frame. PTEN-Long is a membrane-permeable lipid phosphatase that is secreted from cells and can enter other cells. As an exogenous agent, PTEN-Long antagonized PI3K signaling and induced tumor cell death in vitro and in vivo. By providing a means to restore a functional tumor-suppressor protein to tumor cells, PTEN-Long may have therapeutic uses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935617/" 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/PMC3935617/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hopkins, Benjamin D -- Fine, Barry -- Steinbach, Nicole -- Dendy, Meaghan -- Rapp, Zachary -- Shaw, Jacquelyn -- Pappas, Kyrie -- Yu, Jennifer S -- Hodakoski, Cindy -- Mense, Sarah -- Klein, Joshua -- Pegno, Sarah -- Sulis, Maria-Luisa -- Goldstein, Hannah -- Amendolara, Benjamin -- Lei, Liang -- Maurer, Matthew -- Bruce, Jeffrey -- Canoll, Peter -- Hibshoosh, Hanina -- Parsons, Ramon -- 2T32 CA09503/CA/NCI NIH HHS/ -- CA082783/CA/NCI NIH HHS/ -- CA097403/CA/NCI NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- R01 CA082783/CA/NCI NIH HHS/ -- R01 CA155117/CA/NCI NIH HHS/ -- R01 NS066955/NS/NINDS NIH HHS/ -- R01 NS073610/NS/NINDS NIH HHS/ -- R01NS066955/NS/NINDS NIH HHS/ -- T32 CA009503/CA/NCI NIH HHS/ -- T32 GM008224/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):399-402. doi: 10.1126/science.1234907. Epub 2013 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744781" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line, Tumor ; *Cell Survival ; Embryonic Stem Cells ; Glioblastoma/drug therapy/metabolism/pathology ; HEK293 Cells ; Humans ; Mice ; Mice, Nude ; Molecular Sequence Data ; Mutation ; PTEN Phosphohydrolase/*chemistry/genetics/*metabolism/pharmacology ; Peptide Chain Initiation, Translational ; Phosphatidylinositol 3-Kinase/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Messenger/genetics/metabolism ; *Signal Transduction/drug effects ; Xenograft Model Antitumor Assays
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  • 80
    Publication Date: 2013-02-23
    Description: Cellular growth signals stimulate anabolic processes. The mechanistic target of rapamycin complex 1 (mTORC1) is a protein kinase that senses growth signals to regulate anabolic growth and proliferation. Activation of mTORC1 led to the acute stimulation of metabolic flux through the de novo pyrimidine synthesis pathway. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. Growth signaling through mTORC1 thus stimulates the production of new nucleotides to accommodate an increase in RNA and DNA synthesis needed for ribosome biogenesis and anabolic growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753690/" 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/PMC3753690/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ben-Sahra, Issam -- Howell, Jessica J -- Asara, John M -- Manning, Brendan D -- F32 DK095508/DK/NIDDK NIH HHS/ -- F32-DK095508/DK/NIDDK NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P01-CA120964/CA/NCI NIH HHS/ -- P30 CA006516/CA/NCI NIH HHS/ -- P30-CA006516/CA/NCI NIH HHS/ -- R01 CA122617/CA/NCI NIH HHS/ -- R01-CA122617/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 15;339(6125):1323-8. doi: 10.1126/science.1228792. Epub 2013 Feb 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23429703" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Animals ; Aspartate Carbamoyltransferase/*metabolism ; Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)/*metabolism ; Dihydroorotase/*metabolism ; HeLa Cells ; Humans ; Mice ; Multiprotein Complexes/*metabolism ; Pyrimidines/*biosynthesis ; Ribosomal Protein S6 Kinases/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; Tumor Suppressor Proteins/genetics/metabolism
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  • 81
    Publication Date: 2013-05-04
    Description: Superoxide and other reactive oxygen species (ROS) originate from several natural sources and profoundly influence numerous elemental cycles, including carbon and trace metals. In the deep ocean, the permanent absence of light precludes currently known ROS sources, yet ROS production mysteriously occurs. Here, we show that taxonomically and ecologically diverse heterotrophic bacteria from aquatic and terrestrial environments are a vast, unrecognized, and light-independent source of superoxide, and perhaps other ROS derived from superoxide. Superoxide production by a model bacterium within the ubiquitous Roseobacter clade involves an extracellular oxidoreductase that is stimulated by the reduced form of nicotinamide adenine dinucleotide (NADH), suggesting a surprising homology with eukaryotic organisms. The consequences of ROS cycling in immense aphotic zones representing key sites of nutrient regeneration and carbon export must now be considered, including potential control of carbon remineralization and metal bioavailability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diaz, Julia M -- Hansel, Colleen M -- Voelker, Bettina M -- Mendes, Chantal M -- Andeer, Peter F -- Zhang, Tong -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1223-6. doi: 10.1126/science.1237331. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641059" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Carbon Cycle ; *Heterotrophic Processes ; Mercury/*metabolism ; Molecular Sequence Data ; NAD/metabolism ; Oxidoreductases/metabolism ; Phylogeny ; Roseobacter/classification/*metabolism ; Superoxides/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 82
    Publication Date: 2013-03-23
    Description: Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanji, Hiromi -- Ohto, Umeharu -- Shibata, Takuma -- Miyake, Kensuke -- Shimizu, Toshiyuki -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520111" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Imidazoles/chemistry/*metabolism ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Quinolines/chemistry/*metabolism ; Signal Transduction ; Thiazoles/chemistry/*metabolism ; Toll-Like Receptor 8/*agonists/*chemistry/metabolism
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  • 83
    Publication Date: 2013-05-11
    Description: Differences in biomolecular sequence and function underlie dramatic ranges of appearance and behavior among species. We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs. Metazoans have a higher proportion of heteromeric bZIP interactions and more network complexity than the single-cell species. The metazoan bZIP interactomes have broadly similar structures, but there has been extensive rewiring of connections compared to the last common ancestor, and each species network is highly distinct. Many metazoan bZIP orthologs and paralogs have strikingly different interaction specificities, and some differences arise from minor sequence changes. Our data show that a shifting landscape of biochemical functions related to signaling and gene expression contributes to species diversity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115154/" 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/PMC4115154/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reinke, Aaron W -- Baek, Jiyeon -- Ashenberg, Orr -- Keating, Amy E -- GM067681/GM/NIGMS NIH HHS/ -- R01 GM067681/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 May 10;340(6133):730-4. doi: 10.1126/science.1233465.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology, Department of Biology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661758" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Basic-Leucine Zipper Transcription Factors/chemistry/genetics/*metabolism ; Conserved Sequence ; *Evolution, Molecular ; Humans ; *Metabolic Networks and Pathways ; Molecular Sequence Data ; Protein Multimerization
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  • 84
    Publication Date: 2013-03-09
    Description: A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1alpha and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu(230), located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799917/" 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/PMC3799917/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hubbard, Basil P -- Gomes, Ana P -- Dai, Han -- Li, Jun -- Case, April W -- Considine, Thomas -- Riera, Thomas V -- Lee, Jessica E -- E, Sook Yen -- Lamming, Dudley W -- Pentelute, Bradley L -- Schuman, Eli R -- Stevens, Linda A -- Ling, Alvin J Y -- Armour, Sean M -- Michan, Shaday -- Zhao, Huizhen -- Jiang, Yong -- Sweitzer, Sharon M -- Blum, Charles A -- Disch, Jeremy S -- Ng, Pui Yee -- Howitz, Konrad T -- Rolo, Anabela P -- Hamuro, Yoshitomo -- Moss, Joel -- Perni, Robert B -- Ellis, James L -- Vlasuk, George P -- Sinclair, David A -- P01 AG027916/AG/NIA NIH HHS/ -- R01 AG019719/AG/NIA NIH HHS/ -- R01 AG028730/AG/NIA NIH HHS/ -- R37 AG028730/AG/NIA NIH HHS/ -- ZIA HL000659-20/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 8;339(6124):1216-9. doi: 10.1126/science.1231097.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23471411" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Motifs ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Cells, Cultured ; Enzyme Activation ; Forkhead Transcription Factors/chemistry/genetics ; Glutamic Acid/chemistry/genetics ; Heterocyclic Compounds with 4 or More Rings/chemistry/pharmacology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Mice ; Molecular Sequence Data ; Myoblasts/drug effects/enzymology ; Protein Structure, Tertiary ; Sirtuin 1/*chemistry/genetics/*metabolism ; Stilbenes/chemistry/*pharmacology ; Substrate Specificity
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  • 85
    Publication Date: 2013-03-30
    Description: Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the maturation of yeast mating pheromone a-factor. The Ste24p core structure is a ring of seven transmembrane helices enclosing a voluminous cavity containing the active site and substrate-binding groove. The cavity is accessible to the external milieu by means of gaps between splayed transmembrane helices. We hypothesize that cleavage proceeds by means of a processive mechanism of substrate insertion, translocation, and ejection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136949/" 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/PMC4136949/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pryor, Edward E Jr -- Horanyi, Peter S -- Clark, Kathleen M -- Fedoriw, Nadia -- Connelly, Sara M -- Koszelak-Rosenblum, Mary -- Zhu, Guangyu -- Malkowski, Michael G -- Wiener, Michael C -- Dumont, Mark E -- P30 CA044579/CA/NCI NIH HHS/ -- U54 GM094611/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1600-4. doi: 10.1126/science.1232048.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Membrane Protein Structural Biology Consortium, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539602" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Cell Membrane/*enzymology ; Crystallography, X-Ray ; Membrane Proteins/*chemistry ; Metalloendopeptidases/*chemistry ; Molecular Sequence Data ; Protein Structure, Secondary ; Saccharomyces cerevisiae Proteins/*chemistry ; Substrate Specificity
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  • 86
    Publication Date: 2013-10-26
    Description: The quiescent center (QC) plays an essential role during root development by creating a microenvironment that preserves the stem cell fate of its surrounding cells. Despite being surrounded by highly mitotic active cells, QC cells self-renew at a low proliferation rate. Here, we identified the ERF115 transcription factor as a rate-limiting factor of QC cell division, acting as a transcriptional activator of the phytosulfokine PSK5 peptide hormone. ERF115 marks QC cell division but is restrained through proteolysis by the APC/C(CCS52A2) ubiquitin ligase, whereas QC proliferation is driven by brassinosteroid-dependent ERF115 expression. Together, these two antagonistic mechanisms delimit ERF115 activity, which is called upon when surrounding stem cells are damaged, revealing a cell cycle regulatory mechanism accounting for stem cell niche longevity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heyman, Jefri -- Cools, Toon -- Vandenbussche, Filip -- Heyndrickx, Ken S -- Van Leene, Jelle -- Vercauteren, Ilse -- Vanderauwera, Sandy -- Vandepoele, Klaas -- De Jaeger, Geert -- Van Der Straeten, Dominique -- De Veylder, Lieven -- New York, N.Y. -- Science. 2013 Nov 15;342(6160):860-3. doi: 10.1126/science.1240667. Epub 2013 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Systems Biology, VIB, B-9052 Gent, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24158907" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase-Promoting Complex-Cyclosome/metabolism ; Arabidopsis/*cytology/*growth & development ; Arabidopsis Proteins/genetics/*metabolism ; Cell Cycle/genetics/physiology ; Cell Cycle Proteins/metabolism ; Cell Division/genetics/*physiology ; Mitosis/genetics/physiology ; Peptide Hormones/genetics/metabolism ; Plant Roots/*cytology/*growth & development ; Proteolysis ; Signal Transduction ; Stem Cell Niche ; Stem Cells/*physiology ; Transcription Factors/genetics/*metabolism
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  • 87
    Publication Date: 2013-03-30
    Description: Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders. ZMPSTE24 processes prelamin A, a component of the nuclear lamina intermediate filaments, by cleaving it at two sites. Failure of this processing results in accumulation of farnesylated, membrane-associated prelamin A. The 3.4 angstrom crystal structure of human ZMPSTE24 has a seven transmembrane alpha-helical barrel structure, surrounding a large, water-filled, intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic site facing into the chamber. The 3.8 angstrom structure of a complex with a CSIM tetrapeptide showed that the mode of binding of the substrate resembles that of an insect metalloprotease inhibitor in thermolysin. Laminopathy-associated mutations predicted to reduce ZMPSTE24 activity map to the zinc metalloprotease peptide-binding site and to the bottom of the chamber.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quigley, Andrew -- Dong, Yin Yao -- Pike, Ashley C W -- Dong, Liang -- Shrestha, Leela -- Berridge, Georgina -- Stansfeld, Phillip J -- Sansom, Mark S P -- Edwards, Aled M -- Bountra, Chas -- von Delft, Frank -- Bullock, Alex N -- Burgess-Brown, Nicola A -- Carpenter, Elisabeth P -- 092809/Wellcome Trust/United Kingdom -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1604-7. doi: 10.1126/science.1231513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539603" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Lamin Type A ; Membrane Proteins/*chemistry/genetics ; Metabolism, Inborn Errors/genetics/*metabolism ; Metalloendopeptidases/*chemistry/genetics ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics/*metabolism ; Progeria/genetics/metabolism ; Protein Conformation ; Protein Precursors/chemistry/genetics/*metabolism ; Substrate Specificity ; Thermolysin/chemistry
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  • 88
    Publication Date: 2013-08-03
    Description: The posttranslational modification of proteins and their regulation by metabolites represent conserved mechanisms in biology. At the confluence of these two processes, we report that the primary glycolytic intermediate 1,3-bisphosphoglycerate (1,3-BPG) reacts with select lysine residues in proteins to form 3-phosphoglyceryl-lysine (pgK). This reaction, which does not require enzyme catalysis, but rather exploits the electrophilicity of 1,3-BPG, was found by proteomic profiling to be enriched on diverse classes of proteins and prominently in or around the active sites of glycolytic enzymes. pgK modifications inhibit glycolytic enzymes and, in cells exposed to high glucose, accumulate on these enzymes to create a potential feedback mechanism that contributes to the buildup and redirection of glycolytic intermediates to alternate biosynthetic pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005992/" 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/PMC4005992/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moellering, Raymond E -- Cravatt, Benjamin F -- CA087660/CA/NCI NIH HHS/ -- R37 CA087660/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):549-53. doi: 10.1126/science.1238327.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. rmoeller@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23908237" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biomarkers, Tumor/chemistry/metabolism ; Catalysis ; Cell Line ; DNA-Binding Proteins/chemistry/metabolism ; Diphosphoglyceric Acids/*metabolism ; Glucose/metabolism ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/chemistry/metabolism ; Glycerophosphates/*metabolism ; *Glycolysis ; Humans ; Lysine/*analogs & derivatives/*metabolism ; Mice ; Molecular Sequence Data ; Phosphopyruvate Hydratase/chemistry/metabolism ; *Protein Processing, Post-Translational ; Proteins/chemistry/*metabolism ; Tumor Suppressor Proteins/chemistry/metabolism
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  • 89
    Publication Date: 2013-05-04
    Description: In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type alpha-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies showed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ying -- Zhang, Qianyi -- Kong, Huihui -- Jiang, Yongping -- Gao, Yuwei -- Deng, Guohua -- Shi, Jianzhong -- Tian, Guobin -- Liu, Liling -- Liu, Jinxiong -- Guan, Yuntao -- Bu, Zhigao -- Chen, Hualan -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1459-63. doi: 10.1126/science.1229455. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641061" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Brain/virology ; Cell Line ; Ferrets ; Genes, Viral ; Guinea Pigs ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics ; Humans ; Influenza A Virus, H1N1 Subtype/*genetics/pathogenicity ; Influenza A Virus, H5N1 Subtype/*genetics/pathogenicity ; Influenza, Human/transmission/virology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Mutation ; Orthomyxoviridae Infections/*transmission/*virology ; Reassortant Viruses/*genetics/*pathogenicity ; Receptors, Cell Surface/metabolism ; Receptors, Virus/metabolism ; Respiratory System/*virology ; Reverse Genetics ; Ribonucleoproteins/metabolism ; Viral Proteins/genetics/metabolism ; Virus Replication
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  • 90
    Publication Date: 2013-04-13
    Description: Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884217/" 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/PMC3884217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rock, Jeremy M -- Lim, Daniel -- Stach, Lasse -- Ogrodowicz, Roksana W -- Keck, Jamie M -- Jones, Michele H -- Wong, Catherine C L -- Yates, John R 3rd -- Winey, Mark -- Smerdon, Stephen J -- Yaffe, Michael B -- Amon, Angelika -- CA112967/CA/NCI NIH HHS/ -- ES015339/ES/NIEHS NIH HHS/ -- F32 GM086038/GM/NIGMS NIH HHS/ -- GM056800/GM/NIGMS NIH HHS/ -- GM51312/GM/NIGMS NIH HHS/ -- MC_U117584228/Medical Research Council/United Kingdom -- P30 CA014051/CA/NCI NIH HHS/ -- P41 GM103533/GM/NIGMS NIH HHS/ -- P41 RR011823/RR/NCRR NIH HHS/ -- R01 ES015339/ES/NIEHS NIH HHS/ -- R01 GM051312/GM/NIGMS NIH HHS/ -- R01 GM056800/GM/NIGMS NIH HHS/ -- R29 GM056800/GM/NIGMS NIH HHS/ -- U117584228/Medical Research Council/United Kingdom -- U54 CA112967/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 May 17;340(6134):871-5. doi: 10.1126/science.1235822. Epub 2013 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23579499" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; Cell Cycle Proteins/chemistry/*metabolism ; Deoxyribonucleases/chemistry/*metabolism ; Enzyme Activation ; GTP-Binding Proteins/*metabolism ; *Mitosis ; Phosphoproteins/chemistry/*metabolism ; Phosphorylation ; Protein Conformation ; Protein-Serine-Threonine Kinases/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Signal Transduction ; tRNA Methyltransferases/chemistry/*metabolism
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  • 91
    Publication Date: 2013-02-23
    Description: Foreign particles and cells are cleared from the body by phagocytes that must also recognize and avoid clearance of "self" cells. The membrane protein CD47 is reportedly a "marker of self" in mice that impedes phagocytosis of self by signaling through the phagocyte receptor CD172a. Minimal "Self" peptides were computationally designed from human CD47 and then synthesized and attached to virus-size particles for intravenous injection into mice that express a CD172a variant compatible with hCD47. Self peptides delay macrophage-mediated clearance of nanoparticles, which promotes persistent circulation that enhances dye and drug delivery to tumors. Self-peptide affinity for CD172a is near the optimum measured for human CD172a variants, and Self peptide also potently inhibits nanoparticle uptake mediated by the contractile cytoskeleton. The reductionist approach reveals the importance of human Self peptides and their utility in enhancing drug delivery and imaging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966479/" 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/PMC3966479/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rodriguez, Pia L -- Harada, Takamasa -- Christian, David A -- Pantano, Diego A -- Tsai, Richard K -- Discher, Dennis E -- 8UL1TR000003/TR/NCATS NIH HHS/ -- P01-DK032094/DK/NIDDK NIH HHS/ -- P30-DK090969/DK/NIDDK NIH HHS/ -- R01 EB007049/EB/NIBIB NIH HHS/ -- R01 HL062352/HL/NHLBI NIH HHS/ -- R01-EB007049/EB/NIBIB NIH HHS/ -- R01-HL062352/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 22;339(6122):971-5. doi: 10.1126/science.1229568.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biophysics and NanoBioPolymers Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23430657" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigens, CD47/chemistry/immunology/metabolism ; Antigens, Differentiation/*metabolism ; Antineoplastic Agents/administration & dosage ; Autoantigens ; Blood Circulation ; Diagnostic Imaging/methods ; Drug Delivery Systems/*methods ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; *Nanoparticles/administration & dosage/analysis ; Neoplasms/chemistry/diagnosis/drug therapy ; Paclitaxel/administration & dosage ; Particle Size ; Peptide Fragments/chemical synthesis/chemistry/immunology/*metabolism ; Phagocytes/immunology/metabolism ; *Phagocytosis ; Receptors, Immunologic/immunology/*metabolism ; Signal Transduction
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  • 92
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-04-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Mitch -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):27. doi: 10.1126/science.340.6128.27.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23559233" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Guanylate Kinase/*chemistry/*genetics ; Humans ; Neoplasms/enzymology ; Neurons/*enzymology ; Protein Structure, Secondary ; *Pseudogenes
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  • 93
    Publication Date: 2013-01-05
    Description: The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815447/" 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/PMC3815447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ernst, Andreas -- Avvakumov, George -- Tong, Jiefei -- Fan, Yihui -- Zhao, Yanling -- Alberts, Philipp -- Persaud, Avinash -- Walker, John R -- Neculai, Ana-Mirela -- Neculai, Dante -- Vorobyov, Andrew -- Garg, Pankaj -- Beatty, Linda -- Chan, Pak-Kei -- Juang, Yu-Chi -- Landry, Marie-Claude -- Yeh, Christina -- Zeqiraj, Elton -- Karamboulas, Konstantina -- Allali-Hassani, Abdellah -- Vedadi, Masoud -- Tyers, Mike -- Moffat, Jason -- Sicheri, Frank -- Pelletier, Laurence -- Durocher, Daniel -- Raught, Brian -- Rotin, Daniela -- Yang, Jianhua -- Moran, Michael F -- Dhe-Paganon, Sirano -- Sidhu, Sachdev S -- 092076/Wellcome Trust/United Kingdom -- 092381/Wellcome Trust/United Kingdom -- 1R01NS072420-01/Canadian Institutes of Health Research/Canada -- MOP-102536/Canadian Institutes of Health Research/Canada -- MOP-111149/Canadian Institutes of Health Research/Canada -- MOP-13494/Canadian Institutes of Health Research/Canada -- MOP-57795/Canadian Institutes of Health Research/Canada -- R01 NS072420/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):590-5. doi: 10.1126/science.1230161. Epub 2013 Jan 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23287719" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Combinatorial Chemistry Techniques ; Conserved Sequence ; Drug Design ; Endopeptidases/chemistry/*metabolism ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Protease Inhibitors/chemistry/*isolation & purification/pharmacology ; Protein Conformation ; Protein Structure, Secondary ; Small Molecule Libraries ; Ubiquitin/chemistry/genetics/*metabolism ; Ubiquitin Thiolesterase/chemistry/*metabolism ; Ubiquitin-Conjugating Enzymes/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitination/*drug effects
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  • 94
    Publication Date: 2013-03-30
    Description: Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689846/" 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/PMC3689846/" 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 -- Julien, Jean-Philippe -- Menis, Sergey -- Ota, Takayuki -- Kalyuzhniy, Oleksandr -- McGuire, Andrew -- Sok, Devin -- Huang, Po-Ssu -- MacPherson, Skye -- Jones, Meaghan -- Nieusma, Travis -- Mathison, John -- Baker, David -- Ward, Andrew B -- Burton, Dennis R -- Stamatatos, Leonidas -- Nemazee, David -- Wilson, Ian A -- Schief, William R -- 5T32AI007606-10/AI/NIAID NIH HHS/ -- AI081625/AI/NIAID NIH HHS/ -- AI33292/AI/NIAID NIH HHS/ -- AI84817/AI/NIAID NIH HHS/ -- P01 AI094419/AI/NIAID NIH HHS/ -- P30 AI027767-24/AI/NIAID NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R01 AI033292/AI/NIAID NIH HHS/ -- R01 AI073148/AI/NIAID NIH HHS/ -- R01 AI081625/AI/NIAID NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- R37 AI033292/AI/NIAID NIH HHS/ -- T32 CA080416/CA/NCI NIH HHS/ -- T32CA080416/CA/NCI NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 May 10;340(6133):711-6. doi: 10.1126/science.1234150. Epub 2013 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539181" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/genetics/*immunology ; Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Antigens, CD4/immunology ; B-Lymphocytes/immunology ; Crystallography, X-Ray ; DNA Mutational Analysis ; Germ Cells/*immunology ; HIV Envelope Protein gp120/chemistry/genetics/*immunology ; HIV Infections/*prevention & control ; HIV-1/*immunology ; Humans ; Macaca ; Mice ; Models, Animal ; Molecular Sequence Data ; Nanoparticles ; Protein Engineering ; Protein Structure, Tertiary ; Receptors, Antigen, B-Cell/*immunology
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  • 95
    Publication Date: 2013-02-02
    Description: Although much has been done to elucidate the biochemistry of signal transduction and gene regulatory pathways, it remains difficult to understand or predict quantitative responses. We integrate single-cell experiments with stochastic analyses, to identify predictive models of transcriptional dynamics for the osmotic stress response pathway in Saccharomyces cerevisiae. We generate models with varying complexity and use parameter estimation and cross-validation analyses to select the most predictive model. This model yields insight into several dynamical features, including multistep regulation and switchlike activation for several osmosensitive genes. Furthermore, the model correctly predicts the transcriptional dynamics of cells in response to different environmental and genetic perturbations. Because our approach is general, it should facilitate a predictive understanding for signal-activated transcription of other genes in other pathways or organisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751578/" 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/PMC3751578/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neuert, Gregor -- Munsky, Brian -- Tan, Rui Zhen -- Teytelman, Leonid -- Khammash, Mustafa -- van Oudenaarden, Alexander -- 1DP1OD003936/OD/NIH HHS/ -- DP1 CA174420/CA/NCI NIH HHS/ -- U54 CA143874/CA/NCI NIH HHS/ -- U54CA143874/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):584-7. doi: 10.1126/science.1231456.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Physics and Biology and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23372015" target="_blank"〉PubMed〈/a〉
    Keywords: *Gene Expression Regulation, Fungal ; Gene Regulatory Networks ; Heat-Shock Proteins/metabolism ; Membrane Transport Proteins/metabolism ; *Models, Genetic ; *Models, Statistical ; Osmosis ; Osmotic Pressure ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Signal Transduction ; Single-Cell Analysis/*methods ; Stochastic Processes ; *Transcription, Genetic ; *Transcriptional Activation
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  • 96
    Publication Date: 2013-07-28
    Description: The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography-computed tomography scanning and biodistribution analysis using 2-deoxy-2-[18F]fluoro-D-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068965/" 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/PMC4068965/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saeidi, Nima -- Meoli, Luca -- Nestoridi, Eirini -- Gupta, Nitin K -- Kvas, Stephanie -- Kucharczyk, John -- Bonab, Ali A -- Fischman, Alan J -- Yarmush, Martin L -- Stylopoulos, Nicholas -- DK089503/DK/NIDDK NIH HHS/ -- F32 DK095558/DK/NIDDK NIH HHS/ -- F32DK095558/DK/NIDDK NIH HHS/ -- P50 GM021700/GM/NIGMS NIH HHS/ -- T32DK007191/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):406-10. doi: 10.1126/science.1235103.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Basic and Translational Obesity Research, Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888041" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; Blood Glucose/*metabolism ; Cholesterol/biosynthesis ; Diabetes Mellitus, Experimental/metabolism/surgery ; Digestion ; Energy Metabolism ; Fluorodeoxyglucose F18/metabolism ; *Gastric Bypass ; Gene Expression Regulation ; Glucose/*metabolism ; Glucose Transporter Type 1/metabolism ; Glycolysis ; Jejunum/*metabolism ; Male ; Metabolic Networks and Pathways ; Metabolomics ; Multimodal Imaging ; Pentose Phosphate Pathway ; Positron-Emission Tomography ; Rats ; Rats, Long-Evans ; Signal Transduction ; Tissue Distribution ; Tomography, X-Ray Computed ; Up-Regulation
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  • 97
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-01-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forrest, Lucy R -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):399-401. doi: 10.1126/science.1228465.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computational Structural Biology Group, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt am Main, Germany. lucy.forrest@biophys.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349276" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Transport ; Cell Membrane/chemistry ; Ion Channels/chemistry/metabolism ; Membrane Transport Proteins/*chemistry/metabolism ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Secondary
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  • 98
    Publication Date: 2013-11-16
    Description: The mitochondrial uniporter is a highly selective calcium channel in the organelle's inner membrane. Its molecular components include the EF-hand-containing calcium-binding proteins mitochondrial calcium uptake 1 (MICU1) and MICU2 and the pore-forming subunit mitochondrial calcium uniporter (MCU). We sought to achieve a full molecular characterization of the uniporter holocomplex (uniplex). Quantitative mass spectrometry of affinity-purified uniplex recovered MICU1 and MICU2, MCU and its paralog MCUb, and essential MCU regulator (EMRE), a previously uncharacterized protein. EMRE is a 10-kilodalton, metazoan-specific protein with a single transmembrane domain. In its absence, uniporter channel activity was lost despite intact MCU expression and oligomerization. EMRE was required for the interaction of MCU with MICU1 and MICU2. Hence, EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium-conducting role of MCU.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091629/" 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/PMC4091629/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sancak, Yasemin -- Markhard, Andrew L -- Kitami, Toshimori -- Kovacs-Bogdan, Erika -- Kamer, Kimberli J -- Udeshi, Namrata D -- Carr, Steven A -- Chaudhuri, Dipayan -- Clapham, David E -- Li, Andrew A -- Calvo, Sarah E -- Goldberger, Olga -- Mootha, Vamsi K -- DK080261/DK/NIDDK NIH HHS/ -- F32 HL107021/HL/NHLBI NIH HHS/ -- F32HL107021/HL/NHLBI NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- R24 DK080261/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1379-82. doi: 10.1126/science.1242993. Epub 2013 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Massachusetts General Hospital, Department of Systems Biology, Harvard Medical School, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24231807" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calcium Channels/chemistry/genetics/*metabolism ; Calcium-Binding Proteins/genetics/*metabolism ; Cation Transport Proteins/genetics/*metabolism ; Cell Membrane/*metabolism ; EF Hand Motifs ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Mitochondria/*metabolism ; Mitochondrial Membrane Transport Proteins/genetics/*metabolism ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Proteomics
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  • 99
    Publication Date: 2013-02-09
    Description: Methylmercury is a potent neurotoxin produced in natural environments from inorganic mercury by anaerobic bacteria. However, until now the genes and proteins involved have remained unidentified. Here, we report a two-gene cluster, hgcA and hgcB, required for mercury methylation by Desulfovibrio desulfuricans ND132 and Geobacter sulfurreducens PCA. In either bacterium, deletion of hgcA, hgcB, or both genes abolishes mercury methylation. The genes encode a putative corrinoid protein, HgcA, and a 2[4Fe-4S] ferredoxin, HgcB, consistent with roles as a methyl carrier and an electron donor required for corrinoid cofactor reduction, respectively. Among bacteria and archaea with sequenced genomes, gene orthologs are present in confirmed methylators but absent in nonmethylators, suggesting a common mercury methylation pathway in all methylating bacteria and archaea sequenced to date.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parks, Jerry M -- Johs, Alexander -- Podar, Mircea -- Bridou, Romain -- Hurt, Richard A Jr -- Smith, Steven D -- Tomanicek, Stephen J -- Qian, Yun -- Brown, Steven D -- Brandt, Craig C -- Palumbo, Anthony V -- Smith, Jeremy C -- Wall, Judy D -- Elias, Dwayne A -- Liang, Liyuan -- New York, N.Y. -- Science. 2013 Mar 15;339(6125):1332-5. doi: 10.1126/science.1230667. Epub 2013 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393089" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*genetics ; Corrinoids/genetics ; Desulfovibrio desulfuricans/*genetics/metabolism ; Environmental Pollutants/*metabolism ; Ferredoxins/genetics ; Gene Deletion ; Geobacter/*genetics/metabolism ; Mercury/*metabolism ; Methylation ; Molecular Sequence Data ; *Multigene Family
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  • 100
    Publication Date: 2013-08-10
    Description: Brassinosteroids, which control plant growth and development, are sensed by the leucine-rich repeat (LRR) domain of the membrane receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1), but it is unknown how steroid binding at the cell surface activates the cytoplasmic kinase domain of the receptor. A family of somatic embryogenesis receptor kinases (SERKs) has been genetically implicated in mediating early brassinosteroid signaling events. We found a direct and steroid-dependent interaction between the BRI1 and SERK1 LRR domains by analysis of their complex crystal structure at 3.3 angstrom resolution. We show that the SERK1 LRR domain is involved in steroid sensing and, through receptor-co-receptor heteromerization, in the activation of the BRI1 signaling pathway. Our work reveals how known missense mutations in BRI1 and in SERKs modulate brassinosteroid signaling and the targeting mechanism of BRI1 receptor antagonists.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santiago, Julia -- Henzler, Christine -- Hothorn, Michael -- New York, N.Y. -- Science. 2013 Aug 23;341(6148):889-92. doi: 10.1126/science.1242468. Epub 2013 Aug 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Plant Biology Lab, Friedrich Miescher Laboratory of the Max Planck Society, Spemannstrasse 39, Tubingen 72076, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929946" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Brassinosteroids/*metabolism ; Crystallography, X-Ray ; Molecular Sequence Data ; Mutation, Missense ; Protein Kinases/chemistry/genetics/*metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Steroid/*agonists
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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