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  • Amino Acid Sequence  (2,910)
  • American Association for the Advancement of Science (AAAS)  (2,910)
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  • 1
    Publication Date: 2002-04-06
    Description: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" 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/PMC4721576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celeste, Arkady -- Petersen, Simone -- Romanienko, Peter J -- Fernandez-Capetillo, Oscar -- Chen, Hua Tang -- Sedelnikova, Olga A -- Reina-San-Martin, Bernardo -- Coppola, Vincenzo -- Meffre, Eric -- Difilippantonio, Michael J -- Redon, Christophe -- Pilch, Duane R -- Olaru, Alexandru -- Eckhaus, Michael -- Camerini-Otero, R Daniel -- Tessarollo, Lino -- Livak, Ferenc -- Manova, Katia -- Bonner, William M -- Nussenzweig, Michel C -- Nussenzweig, Andre -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):922-7. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934988" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology/physiology ; Base Sequence ; Cell Aging ; Cell Cycle ; Cells, Cultured ; *Chromosome Aberrations ; DNA Damage ; *DNA Repair ; Female ; Gene Targeting ; Histones/chemistry/*genetics/*physiology ; Immunoglobulin Class Switching ; Infertility, Male/genetics/physiopathology ; Lymphocyte Count ; Male ; Meiosis ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Phosphorylation ; *Recombination, Genetic ; Spermatocytes/physiology ; T-Lymphocytes/immunology/physiology
    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: 2002-12-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Funes, Soledad -- Davidson, Edgar -- Reyes-Prieto, Adrian -- Magallon, Susana -- Herion, Pascal -- King, Michael P -- Gonzalez-Halphen, Diego -- HL59646/HL/NHLBI NIH HHS/ -- TW01176/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2155.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico (UNAM), 04510 D.F., Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481129" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apicomplexa/enzymology/*genetics/ultrastructure ; *Biological Evolution ; Cell Nucleus/genetics ; Chlamydomonas reinhardtii/enzymology/genetics ; Chlorophyta/enzymology/*genetics ; Cloning, Molecular ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/chemistry/*genetics ; *Gene Transfer, Horizontal ; Genes ; Genes, Protozoan ; Molecular Sequence Data ; Phylogeny ; Plastids/*genetics ; Symbiosis ; Toxoplasma/enzymology/genetics
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  • 3
    Publication Date: 2002-02-09
    Description: Double-stranded RNA-mediated gene interference (RNAi) in Caenorhabditis elegans systemically inhibits gene expression throughout the organism. To investigate how gene-specific silencing information is transmitted between cells, we constructed a strain that permits visualization of systemic RNAi. We used this strain to identify systemic RNA interference-deficient (sid) loci required to spread gene-silencing information between tissues but not to initiate or maintain an RNAi response. One of these loci, sid-1, encodes a conserved protein with predicted transmembrane domains. SID-1 is expressed in cells sensitive to RNAi, is localized to the cell periphery, and is required cell-autonomously for systemic RNAi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winston, William M -- Molodowitch, Christina -- Hunter, Craig P -- New York, N.Y. -- Science. 2002 Mar 29;295(5564):2456-9. Epub 2002 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834782" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/embryology/*genetics/metabolism ; Caenorhabditis elegans Proteins/chemistry/*genetics/*physiology ; Calmodulin-Binding Proteins/genetics ; Cytoplasm/metabolism ; Embryo, Nonmammalian/physiology ; *Gene Silencing ; Genes, Helminth ; Germ Cells/metabolism ; Green Fluorescent Proteins ; Intestines/metabolism ; Luminescent Proteins/genetics ; Membrane Proteins/chemistry/*genetics/*physiology ; Molecular Sequence Data ; Mosaicism ; Muscle Proteins/genetics ; Muscles/metabolism ; Mutation ; Protein Structure, Tertiary ; RNA, Double-Stranded/*genetics/metabolism ; RNA, Helminth/*genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Transgenes
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  • 4
    Publication Date: 2003-04-26
    Description: Tubular nanostructures are suggested to have a wide range of applications in nanotechnology. We report our observation of the self-assembly of a very short peptide, the Alzheimer's beta-amyloid diphenylalanine structural motif, into discrete and stiff nanotubes. Reduction of ionic silver within the nanotubes, followed by enzymatic degradation of the peptide backbone, resulted in the production of discrete nanowires with a long persistence length. The same dipeptide building block, made of D-phenylalanine, resulted in the production of enzymatically stable nanotubes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reches, Meital -- Gazit, Ehud -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):625-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12714741" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Amyloid beta-Peptides/chemistry ; Biosensing Techniques ; Birefringence ; Dipeptides/*chemistry ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Molecular Sequence Data ; *Nanotechnology ; Oxidation-Reduction ; Protein Conformation ; Silver ; Solubility ; Spectroscopy, Fourier Transform Infrared
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  • 5
    Publication Date: 2002-02-09
    Description: The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gadek, T R -- Burdick, D J -- McDowell, R S -- Stanley, M S -- Marsters, J C Jr -- Paris, K J -- Oare, D A -- Reynolds, M E -- Ladner, C -- Zioncheck, K A -- Lee, W P -- Gribling, P -- Dennis, M S -- Skelton, N J -- Tumas, D B -- Clark, K R -- Keating, S M -- Beresini, M H -- Tilley, J W -- Presta, L G -- Bodary, S C -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1086-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioorganic Chemistry, Genentech, One DNA Way, South San Francisco, CA 94080, USA. trg@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834839" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical ; synthesis/chemistry/metabolism/pharmacology ; Cyclosporine/pharmacology ; Dermatitis, Irritant/drug therapy ; Dinitrofluorobenzene ; Drug Design ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Female ; Humans ; Immunoglobulin Fab Fragments/immunology/pharmacology ; Immunosuppressive Agents/chemical synthesis/chemistry/metabolism/*pharmacology ; Intercellular Adhesion Molecule-1/chemistry/*immunology/*metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Mutagenesis ; Protein Structure, Secondary ; Structure-Activity Relationship ; Thiophenes/*chemical synthesis/chemistry/metabolism/*pharmacology ; beta-Alanine/analogs & derivatives/*chemical ; synthesis/chemistry/metabolism/*pharmacology
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  • 6
    Publication Date: 2002-02-09
    Description: Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rezaie, Tayebeh -- Child, Anne -- Hitchings, Roger -- Brice, Glen -- Miller, Lauri -- Coca-Prados, Miguel -- Heon, Elise -- Krupin, Theodore -- Ritch, Robert -- Kreutzer, Donald -- Crick, R Pitts -- Sarfarazi, Mansoor -- EY-09947/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1077-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834836" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alternative Splicing ; Amino Acid Sequence ; Brain/metabolism ; Chromosome Mapping ; Chromosomes, Human, Pair 10/genetics ; Ciliary Body/metabolism ; Exons ; Eye Proteins/analysis/chemistry/*genetics/physiology ; Female ; Glaucoma, Open-Angle/*genetics ; Golgi Apparatus/chemistry ; Heterozygote ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; *Mutation ; *Mutation, Missense ; Nerve Tissue Proteins/analysis/chemistry/*genetics/physiology ; Ocular Hypertension/genetics ; Pedigree ; Polymorphism, Single-Stranded Conformational ; Retina/metabolism ; Trabecular Meshwork/metabolism ; *Transcription Factor TFIIIA ; Zinc Fingers
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  • 7
    Publication Date: 2002-04-27
    Description: Little is known of how plant disease resistance (R) proteins recognize pathogens and activate plant defenses. Rcr3 is specifically required for the function of Cf-2, a Lycopersicon pimpinellifolium gene bred into cultivated tomato (Lycopersicon esculentum) for resistance to Cladosporium fulvum. Rcr3 encodes a secreted papain-like cysteine endoprotease. Genetic analysis shows Rcr3 is allelic to the L. pimpinellifolium Ne gene, which suppresses the Cf-2-dependent autonecrosis conditioned by its L. esculentum allele, ne (necrosis). Rcr3 alleles from these two species encode proteins that differ by only seven amino acids. Possible roles of Rcr3 in Cf-2-dependent defense and autonecrosis are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruger, Julia -- Thomas, Colwyn M -- Golstein, Catherine -- Dixon, Mark S -- Smoker, Matthew -- Tang, Saijun -- Mulder, Lonneke -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2002 Apr 26;296(5568):744-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Sainsbury Laboratory, John Innes Centre, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11976458" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Cladosporium/*physiology ; Cloning, Molecular ; Cysteine Endopeptidases/chemistry/*genetics/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Gene Expression Regulation, Plant ; *Genes, Plant ; Immunity, Innate ; Leucine/analogs & derivatives/pharmacology ; Lycopersicon esculentum/*enzymology/genetics/*microbiology/physiology ; Molecular Sequence Data ; Mutation ; Phenotype ; *Plant Diseases ; Plant Leaves/enzymology ; Plant Proteins/*metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/chemistry/metabolism ; Tobacco/genetics ; Transgenes
    Print ISSN: 0036-8075
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  • 8
    Publication Date: 2002-04-06
    Description: The conserved Sir2 family of proteins has protein deacetylase activity that is dependent on NAD (the oxidized form of nicotinamide adenine dinucleotide). Although histones are one likely target for the enzymatic activity of eukaryotic Sir2 proteins, little is known about the substrates and roles of prokaryotic Sir2 homologs. We reveal that an archaeal Sir2 homolog interacts specifically with the major archaeal chromatin protein, Alba, and that Alba exists in acetylated and nonacetylated forms. Furthermore, we show that Sir2 can deacetylate Alba and mediate transcriptional repression in a reconstituted in vitro transcription system. These data provide a paradigm for how Sir2 family proteins influence transcription and suggest that modulation of chromatin structure by acetylation arose before the divergence of the archaeal and eukaryotic lineages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, Stephen D -- Botting, Catherine H -- Wardleworth, Benjamin N -- Jackson, Stephen P -- White, Malcolm F -- New York, N.Y. -- Science. 2002 Apr 5;296(5565):148-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Cancer Cell Unit, The Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 2QH, UK. sdb@mole.bio.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11935028" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Archaeal Proteins/*chemistry/*metabolism ; Chromatin/*metabolism ; DNA/metabolism ; Gene Expression Regulation, Archaeal ; Histone Deacetylases/chemistry/*metabolism ; Molecular Sequence Data ; Molecular Weight ; Protein Binding ; Recombinant Fusion Proteins/chemistry/metabolism ; *Silent Information Regulator Proteins, Saccharomyces cerevisiae ; Sirtuin 2 ; Sirtuins ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sulfolobus/*chemistry/genetics/metabolism ; Templates, Genetic ; Trans-Activators/chemistry/*metabolism ; Transcription, Genetic
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-02-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Calladine, C R -- Pratap, V -- Chandran, V -- Mizuguchi, K -- Luisi, B F -- New York, N.Y. -- Science. 2003 Jan 31;299(5607):661-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12561825" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Escherichia coli Proteins/*chemistry ; Glycine/chemistry ; Ion Channels/*chemistry ; *Models, Molecular ; Protein Conformation ; Protein Structure, Secondary
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-03-01
    Description: Although curvature of biological surfaces has been considered from mathematical and biophysical perspectives, its molecular and developmental basis is unclear. We have studied the cin mutant of Antirrhinum, which has crinkly rather than flat leaves. Leaves of cin display excess growth in marginal regions, resulting in a gradual introduction of negative curvature during development. This reflects a change in the shape and the progression of a cell-cycle arrest front moving from the leaf tip toward the base. CIN encodes a TCP protein and is expressed downstream of the arrest front. We propose that CIN promotes zero curvature (flatness) by making cells more sensitive to an arrest signal, particularly in marginal regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nath, Utpal -- Crawford, Brian C W -- Carpenter, Rosemary -- Coen, Enrico -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1404-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610308" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antirrhinum/cytology/*genetics/*growth & development/metabolism ; Base Sequence ; Cell Cycle ; Cell Differentiation ; Cell Division ; Cell Size ; Cyclin D3 ; Cyclins/genetics/metabolism ; Gene Deletion ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Histones/genetics/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Mutation ; Plant Leaves/anatomy & histology/cytology/*growth & development/metabolism ; Plant Proteins/chemistry/genetics/metabolism ; Surface Properties ; Transcription Factors/chemistry/genetics/*metabolism
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  • 11
    Publication Date: 2003-06-14
    Description: In eukaryotes, the combinatorial association of sequence-specific DNA binding proteins is essential for transcription. We have used protein arrays to test 492 pairings of a nearly complete set of coiled-coil strands from human basic-region leucine zipper (bZIP) transcription factors. We find considerable partnering selectivity despite the bZIPs' homologous sequences. The interaction data are of high quality, as assessed by their reproducibility, reciprocity, and agreement with previous observations. Biophysical studies in solution support the relative binding strengths observed with the arrays. New associations provide insights into the circadian clock and the unfolded protein response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newman, John R S -- Keating, Amy E -- New York, N.Y. -- Science. 2003 Jun 27;300(5628):2097-101. Epub 2003 Jun 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805554" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Basic-Leucine Zipper Transcription Factors ; Chromatography, High Pressure Liquid ; Circadian Rhythm ; Circular Dichroism ; Cyclic AMP Response Element-Binding Protein/chemistry/metabolism ; DNA-Binding Proteins/chemistry/isolation & purification/*metabolism ; Dimerization ; G-Box Binding Factors ; Humans ; *Leucine Zippers ; Peptides/chemistry/isolation & purification/metabolism ; *Protein Array Analysis ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; Signal Transduction ; Temperature ; Thermodynamics ; Transcription Factors/*chemistry/isolation & purification/*metabolism
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  • 12
    Publication Date: 2003-07-19
    Description: We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. Nipponbare. Through homology searches of publicly available sequence data, we assigned tentative protein functions to 21,596 clones (75.86%). Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome. Protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis. Sixty-four percent of our cDNAs are homologous to Arabidopsis proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice Full-Length cDNA Consortium -- National Institute of Agrobiological Sciences Rice Full-Length cDNA Project Team -- Kikuchi, Shoshi -- Satoh, Kouji -- Nagata, Toshifumi -- Kawagashira, Nobuyuki -- Doi, Koji -- Kishimoto, Naoki -- Yazaki, Junshi -- Ishikawa, Masahiro -- Yamada, Hitomi -- Ooka, Hisako -- Hotta, Isamu -- Kojima, Keiichi -- Namiki, Takahiro -- Ohneda, Eisuke -- Yahagi, Wataru -- Suzuki, Kohji -- Li, Chao Jie -- Ohtsuki, Kenji -- Shishiki, Toru -- Foundation of Advancement of International Science Genome Sequencing & Analysis Group -- Otomo, Yasuhiro -- Murakami, Kazuo -- Iida, Yoshiharu -- Sugano, Sumio -- Fujimura, Tatsuto -- Suzuki, Yutaka -- Tsunoda, Yuki -- Kurosaki, Takashi -- Kodama, Takeko -- Masuda, Hiromi -- Kobayashi, Michie -- Xie, Quihong -- Lu, Min -- Narikawa, Ryuya -- Sugiyama, Akio -- Mizuno, Kouichi -- Yokomizo, Satoko -- Niikura, Junko -- Ikeda, Rieko -- Ishibiki, Junya -- Kawamata, Midori -- Yoshimura, Akemi -- Miura, Junichirou -- Kusumegi, Takahiro -- Oka, Mitsuru -- Ryu, Risa -- Ueda, Mariko -- Matsubara, Kenichi -- RIKEN -- Kawai, Jun -- Carninci, Piero -- Adachi, Jun -- Aizawa, Katsunori -- Arakawa, Takahiro -- Fukuda, Shiro -- Hara, Ayako -- Hashizume, Wataru -- Hayatsu, Norihito -- Imotani, Koichi -- Ishii, Yoshiyuki -- Itoh, Masayoshi -- Kagawa, Ikuko -- Kondo, Shinji -- Konno, Hideaki -- Miyazaki, Ai -- Osato, Naoki -- Ota, Yoshimi -- Saito, Rintaro -- Sasaki, Daisuke -- Sato, Kenjiro -- Shibata, Kazuhiro -- Shinagawa, Akira -- Shiraki, Toshiyuki -- Yoshino, Masayasu -- Hayashizaki, Yoshihide -- Yasunishi, Ayako -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):376-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, National Institute of Agrobiological Sciences, 2-1-2 Kannon-dai, Tsukuba, Ibaraki 305-8602, Japan. skikuchi@nias.affrc.go.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12869764" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; Cloning, Molecular ; Computational Biology ; DNA, Complementary ; Databases, Nucleic Acid ; Databases, Protein ; Genes, Plant ; *Genome, Plant ; Molecular Sequence Data ; Open Reading Frames ; Oryza/*genetics ; Plant Proteins/chemistry/genetics/physiology ; Protein Structure, Tertiary ; RNA, Antisense/genetics ; *Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Transcription Factors/chemistry/genetics ; Transcription, Genetic
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-28
    Description: The metabotropic glutamate receptors (mGluRs) are widely distributed in the brain and play important roles in synaptic plasticity. Here it is shown that some types of mGluRs are activated not only by glutamate but also by extracellular Ca2+ (Ca2+o). A single amino acid residue was found to determine the sensitivity of mGluRs to Ca2+o. One of the receptors, mGluR1alpha, but not its point mutant with reduced sensitivity to Ca2+o, caused morphological changes when transfected into mammalian cells. Thus, the sensing of Ca2+o by mGluRs may be important in cells under physiological condition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kubo, Y -- Miyashita, T -- Murata, Y -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1722-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan. ykubo@tmin.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9497291" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/ultrastructure ; Amino Acid Sequence ; Animals ; Binding Sites ; Brain/metabolism ; CHO Cells ; Calcium/*metabolism/pharmacology ; Cell Size ; Cricetinae ; Cyclic AMP/metabolism ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; Glutamic Acid/metabolism/pharmacology ; Molecular Sequence Data ; Oocytes ; Point Mutation ; Potassium Channels/metabolism ; *Potassium Channels, Inwardly Rectifying ; Rats ; Receptors, Metabotropic Glutamate/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Second Messenger Systems ; Transfection ; Xenopus laevis
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  • 14
    Publication Date: 1998-12-16
    Description: A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be alpha-dystroglycan (alpha-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified alpha-DG protein. Soluble alpha-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, alpha-DG is a cellular receptor for both LCMV and LFV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, W -- Henry, M D -- Borrow, P -- Yamada, H -- Elder, J H -- Ravkov, E V -- Nichol, S T -- Compans, R W -- Campbell, K P -- Oldstone, M B -- AG 00080/AG/NIA NIH HHS/ -- AI 09484/AI/NIAID NIH HHS/ -- DK09712/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):2079-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Virology, Department of Neuropharmacology, 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/9851928" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arenavirus/metabolism ; Cell Line ; Cytoskeletal Proteins/chemistry/genetics/*metabolism ; Dystroglycans ; Lassa virus/*metabolism/physiology ; Lymphocytic choriomeningitis virus/*metabolism/physiology ; Membrane Glycoproteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Receptors, Virus/chemistry/*metabolism ; Recombinant Fusion Proteins/metabolism ; Virus Replication
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-29
    Description: After the vertebrate lens is induced from head ectoderm, lens-specific genes are expressed. Transcriptional regulation of the lens-specific alphaA-crystallin gene is controlled by an enhancer element, alphaCE2. A gene encoding an alphaCE2-binding protein, L-maf(lens-specific maf), was isolated. L-maf expression is initiated in the lens placode and is restricted to lens cells. The gene product L-Maf regulates the expression of multiple genes expressed in the lens, and ectopic expression of this transcription factor converts chick embryonic ectodermal cells and cultured cells into lens fibers. Thus, vertebrate lens induction and differentiation can be triggered by the activation of L-Maf.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ogino, H -- Yasuda, K -- New York, N.Y. -- Science. 1998 Apr 3;280(5360):115-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0101, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9525857" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Basic-Leucine Zipper Transcription Factors ; Cell Differentiation ; Cells, Cultured ; Chick Embryo ; Crystallins/genetics ; DNA, Complementary ; DNA-Binding Proteins/chemistry/genetics ; Ectoderm ; Enhancer Elements, Genetic ; Eye Proteins/genetics ; G-Box Binding Factors ; *Gene Expression Regulation, Developmental ; Genes, Reporter ; Intermediate Filament Proteins/genetics ; Lens, Crystalline/*cytology/*embryology/metabolism ; Maf Transcription Factors ; Molecular Sequence Data ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Transfection
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cascalho, M -- Wong, J -- Steinberg, C -- Wabl, M -- 1R01 GM37699/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 20;279(5354):1207-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9469811" target="_blank"〉PubMed〈/a〉
    Keywords: *Adenosine Triphosphatases ; Alleles ; Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Base Composition ; Base Sequence ; Cloning, Molecular ; Crosses, Genetic ; *DNA Repair ; *DNA Repair Enzymes ; *DNA-Binding Proteins ; Female ; Gene Rearrangement ; *Genes, Immunoglobulin ; Heterozygote ; Immunoglobulin Heavy Chains/chemistry/genetics ; Immunoglobulin Variable Region/chemistry/*genetics ; Immunoglobulin lambda-Chains/chemistry/genetics ; Male ; Mice ; Mice, Knockout ; Molecular Sequence Data ; *Mutation ; Proteins/*genetics/physiology
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  • 17
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-10
    Description: The 2.5 angstrom resolution x-ray crystal structure of the Escherichia coli RNA polymerase (RNAP) alpha subunit amino-terminal domain (alphaNTD), which is necessary and sufficient to dimerize and assemble the other RNAP subunits into a transcriptionally active enzyme and contains all of the sequence elements conserved among eukaryotic alpha homologs, has been determined. The alphaNTD monomer comprises two distinct, flexibly linked domains, only one of which participates in the dimer interface. In the alphaNTD dimer, a pair of helices from one monomer interact with the cognate helices of the other to form an extensive hydrophobic core. All of the determinants for interactions with the other RNAP subunits lie on one face of the alphaNTD dimer. Sequence alignments, combined with secondary-structure predictions, support proposals that a heterodimer of the eukaryotic RNAP subunits related to Saccharomyces cerevisiae Rpb3 and Rpb11 plays the role of the alphaNTD dimer in prokaryotic RNAP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, G -- Darst, S A -- GM19441-01/GM/NIGMS NIH HHS/ -- GM53759/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 10;281(5374):262-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9657722" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/*chemistry ; Dimerization ; Escherichia coli/*enzymology ; Models, Molecular ; Molecular Sequence Data ; *Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; RNA Polymerase II/chemistry ; *Saccharomyces cerevisiae Proteins ; Sequence Alignment
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  • 18
    Publication Date: 1998-02-21
    Description: Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4, 5-trisphosphate [PtdIns(3,4,5)P3] and PtdIns(3,4)P2 in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, Thr308-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)P3 and associated with lipid vesicles containing it. These kinases contain an NH2-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)P3 or PtdIns- (3,4)P2 to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, L -- Anderson, K -- Stokoe, D -- Erdjument-Bromage, H -- Painter, G F -- Holmes, A B -- Gaffney, P R -- Reese, C B -- McCormick, F -- Tempst, P -- Coadwell, J -- Hawkins, P T -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1998 Jan 30;279(5351):710-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Inositide Laboratory, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9445477" target="_blank"〉PubMed〈/a〉
    Keywords: 3-Phosphoinositide-Dependent Protein Kinases ; Alternative Splicing ; Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/enzymology ; Cloning, Molecular ; DNA, Complementary ; Drosophila ; Drosophila Proteins ; Enzyme Activation ; Humans ; Liposomes/metabolism ; Molecular Sequence Data ; Open Reading Frames ; Phosphatidylinositol Phosphates/*metabolism ; Phosphorylation ; Platelet-Derived Growth Factor/pharmacology ; Protein-Serine-Threonine Kinases/chemistry/genetics/isolation & ; purification/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-akt ; Rats ; Recombinant Proteins/metabolism ; Sheep ; *Signal Transduction
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  • 19
    Publication Date: 1998-03-21
    Description: Viral infection is sometimes associated with the initiation or exacerbation of autoimmune disease, although the underlying mechanisms remain unclear. One proposed mechanism is that viral determinants that mimic host antigens trigger self-reactive T cell clones to destroy host tissue. An epitope expressed by a coat protein of herpes simplex virus-type 1 (HSV-1) KOS strain has now been shown to be recognized by autoreactive T cells that target corneal antigens in a murine model of autoimmune herpes stromal keratitis. Mutant HSV-1 viruses that lacked this epitope did not induce autoimmune disease. Thus, expression of molecular mimics can influence the development of autoimmune disease after viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Z S -- Granucci, F -- Yeh, L -- Schaffer, P A -- Cantor, H -- AI 37562/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 27;279(5355):1344-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9478893" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Autoantigens/immunology ; Autoimmune Diseases/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Capsid/chemistry/genetics/*immunology ; *Capsid Proteins ; Cornea/*immunology ; Epitopes ; Eye Proteins/immunology ; Herpesvirus 1, Human/*immunology ; Keratitis, Herpetic/*immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; *Molecular Mimicry ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligopeptides/immunology ; Viral Proteins
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-28
    Description: The OxyR transcription factor is sensitive to oxidation and activates the expression of antioxidant genes in response to hydrogen peroxide in Escherichia coli. Genetic and biochemical studies revealed that OxyR is activated through the formation of a disulfide bond and is deactivated by enzymatic reduction with glutaredoxin 1 (Grx1). The gene encoding Grx1 is regulated by OxyR, thus providing a mechanism for autoregulation. The redox potential of OxyR was determined to be -185 millivolts, ensuring that OxyR is reduced in the absence of stress. These results represent an example of redox signaling through disulfide bond formation and reduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, M -- Aslund, F -- Storz, G -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1718-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, 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/9497290" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/genetics/metabolism ; Base Sequence ; Cysteine/metabolism ; *DNA-Binding Proteins ; Disulfides/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins ; Gene Expression Regulation, Bacterial ; Glutaredoxins ; Glutathione/metabolism ; Glutathione Disulfide/metabolism ; Glutathione Reductase/metabolism ; Hydrogen Peroxide/*metabolism/pharmacology ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidative Stress ; *Oxidoreductases ; Proteins/genetics/metabolism ; Repressor Proteins/genetics/*metabolism ; Signal Transduction ; Thioredoxins/metabolism ; Transcription Factors/genetics/*metabolism
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  • 21
    Publication Date: 1998-10-23
    Description: Analysis of the 1,042,519-base pair Chlamydia trachomatis genome revealed unexpected features related to the complex biology of chlamydiae. Although chlamydiae lack many biosynthetic capabilities, they retain functions for performing key steps and interconversions of metabolites obtained from their mammalian host cells. Numerous potential virulence-associated proteins also were characterized. Several eukaryotic chromatin-associated domain proteins were identified, suggesting a eukaryotic-like mechanism for chlamydial nucleoid condensation and decondensation. The phylogenetic mosaic of chlamydial genes, including a large number of genes with phylogenetic origins from eukaryotes, implies a complex evolution for adaptation to obligate intracellular parasitism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, R S -- Kalman, S -- Lammel, C -- Fan, J -- Marathe, R -- Aravind, L -- Mitchell, W -- Olinger, L -- Tatusov, R L -- Zhao, Q -- Koonin, E V -- Davis, R W -- AI 39258/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Oct 23;282(5389):754-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Infectious Diseases, University of California, Berkeley, CA 94720, USA. ctgenome@socrates.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9784136" target="_blank"〉PubMed〈/a〉
    Keywords: Aerobiosis ; Amino Acid Sequence ; Amino Acids/biosynthesis ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Proteins/chemistry/genetics ; Biological Evolution ; Chlamydia trachomatis/classification/*genetics/metabolism/physiology ; DNA Repair ; Energy Metabolism ; Enzymes/chemistry/genetics ; *Genome, Bacterial ; Humans ; Lipids/biosynthesis ; Molecular Sequence Data ; Peptidoglycan/biosynthesis/genetics ; Phylogeny ; Protein Biosynthesis ; Recombination, Genetic ; *Sequence Analysis, DNA ; Transcription, Genetic ; Transformation, Bacterial ; Virulence
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-10
    Description: Recombinant proteins containing four cysteines at the i, i + 1, i + 4, and i + 5 positions of an alpha helix were fluorescently labeled in living cells by extracellular administration of 4',5'-bis(1,3, 2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chemical properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye molecules added from outside the cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffin, B A -- Adams, S R -- Tsien, R Y -- NS27177/NS/NINDS NIH HHS/ -- T32 CA09523/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 10;281(5374):269-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093-0647, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9657724" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calmodulin/chemistry/genetics/metabolism ; Cell Membrane Permeability ; Cell Survival ; Cysteine/*chemistry ; Energy Transfer ; Ethylene Glycol ; Fluoresceins/chemical synthesis/chemistry/*metabolism ; Fluorescence ; *Fluorescent Dyes ; Green Fluorescent Proteins ; HeLa Cells ; Humans ; Jurkat Cells ; Ligands ; Luminescent Proteins/chemistry/genetics/metabolism ; Molecular Sequence Data ; Organometallic Compounds/chemical synthesis/chemistry/*metabolism ; Peptides/chemistry/*metabolism ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/*metabolism ; Spectrometry, Fluorescence ; Transfection
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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22-base pair duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The linker region that connects the central core of the enzyme to the carboxyl-terminal domain assumes a coiled-coil configuration and protrudes away from the remainder of the enzyme. The positively charged DNA-proximal surface of the linker makes only a few contacts with the DNA downstream of the cleavage site. In combination with the crystal structures of the reconstituted human topoisomerase I before and after DNA cleavage, this information suggests which amino acid residues are involved in catalyzing phosphodiester bond breakage and religation. The structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed "controlled rotation."〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stewart, L -- Redinbo, M R -- Qiu, X -- Hol, W G -- Champoux, J J -- CA65656/CA/NCI NIH HHS/ -- GM16713/GM/NIGMS NIH HHS/ -- GM49156/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Mar 6;279(5356):1534-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomolecular Structure Center and Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195-7742, USA. emerald_biostructures@rocketmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9488652" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arginine/chemistry/metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA Topoisomerases, Type I/*chemistry/*metabolism ; Humans ; Hydrogen Bonding ; *Models, Chemical ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/chemistry/metabolism ; *Protein Conformation ; Protein Structure, Secondary ; Tyrosine/chemistry/metabolism
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  • 24
    Publication Date: 1998-11-13
    Description: The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peschon, J J -- Slack, J L -- Reddy, P -- Stocking, K L -- Sunnarborg, S W -- Lee, D C -- Russell, W E -- Castner, B J -- Johnson, R S -- Fitzner, J N -- Boyce, R W -- Nelson, N -- Kozlosky, C J -- Wolfson, M F -- Rauch, C T -- Cerretti, D P -- Paxton, R J -- March, C J -- Black, R A -- CA43793/CA/NCI NIH HHS/ -- DK53804/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1281-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunex Corporation, Seattle, WA 98101, USA. peschon@immunex.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812885" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins ; Amino Acid Sequence ; Animals ; Catalytic Domain ; Cell Membrane/*metabolism ; Cells, Cultured ; Crosses, Genetic ; *Embryonic and Fetal Development ; L-Selectin/metabolism ; Ligands ; Membrane Proteins/*metabolism ; Metalloendopeptidases/chemistry/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Processing, Post-Translational ; Receptors, Tumor Necrosis Factor/metabolism ; Transforming Growth Factor alpha/metabolism ; Tumor Necrosis Factor-alpha/*metabolism
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  • 25
    Publication Date: 1998-03-21
    Description: Long-term potentiation (LTP) is an activity-dependent strengthening of synaptic efficacy that is considered to be a model of learning and memory. Protein tyrosine phosphorylation is necessary to induce LTP. Here, induction of LTP in CA1 pyramidal cells of rats was prevented by blocking the tyrosine kinase Src, and Src activity was increased by stimulation producing LTP. Directly activating Src in the postsynaptic neuron enhanced excitatory synaptic responses, occluding LTP. Src-induced enhancement of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor-mediated synaptic responses required raised intracellular Ca2+ and N-methyl-D-aspartate (NMDA) receptors. Thus, Src activation is necessary and sufficient for inducing LTP and may function by up-regulating NMDA receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Y M -- Roder, J C -- Davidow, J -- Salter, M W -- New York, N.Y. -- Science. 1998 Feb 27;279(5355):1363-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Molecular and Medical Genetics, University of Toronto, M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9478899" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Electric Stimulation ; Enzyme Activation ; Excitatory Postsynaptic Potentials/drug effects ; Hippocampus/cytology/enzymology/*physiology ; In Vitro Techniques ; *Long-Term Potentiation ; Molecular Sequence Data ; Oligopeptides/pharmacology ; Patch-Clamp Techniques ; Peptide Fragments/pharmacology ; Proto-Oncogene Proteins pp60(c-src)/pharmacology ; Pyramidal Cells/enzymology/*physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Recombinant Proteins/pharmacology ; Up-Regulation ; src-Family Kinases/*metabolism
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Feb 13;279(5353):978-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9490484" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Databases, Factual ; *Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Proteins/*chemistry/classification/genetics ; Software
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: Genetic selection was exploited in combination with structure-based design to transform an intimately entwined, dimeric chorismate mutase into a monomeric, four-helix-bundle protein with near native activity. Successful reengineering depended on choosing a thermostable starting protein, introducing point mutations that preferentially destabilize the wild-type dimer, and using directed evolution to optimize an inserted interhelical turn. Contrary to expectations based on studies of other four-helix-bundle proteins, only a small fraction of possible turn sequences (fewer than 0.05 percent) yielded well-behaved, monomeric, and highly active enzymes. Selection for catalytic function thus provides an efficient yet stringent method for rapidly assessing correctly folded polypeptides and may prove generally useful for protein design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacBeath, G -- Kast, P -- Hilvert, D -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1958-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Scripps Research Institute, Department of Chemistry, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9506949" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Catalysis ; Chorismate Mutase/*chemistry/genetics/*metabolism ; Circular Dichroism ; Cloning, Molecular ; Dimerization ; *Directed Molecular Evolution ; Escherichia coli/genetics ; Models, Molecular ; Molecular Sequence Data ; *Protein Conformation ; *Protein Engineering ; Protein Folding ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/metabolism ; Transformation, Bacterial
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-31
    Description: Gamete interactions during fertilization exhibit species specificity. In abalone, the sperm protein lysin species-specifically creates a hole in the egg envelope. Lysin evolves rapidly by positive Darwinian selection. Evolution of the egg receptor for lysin provides the selective pressure for lysin's divergence. The egg receptor for lysin is a tandemly repeated sequence that evolves by concerted evolution. Concerted evolution in the egg receptor could explain the rapid, adaptive evolution in sperm lysin and may provide an underlying molecular mechanism that gives rise to species-specific fertilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swanson, W J -- Vacquier, V D -- HD12986/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 31;281(5377):710-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093-0202, USA. jwswanson@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9685267" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Egg Proteins/chemistry/*genetics/metabolism ; *Evolution, Molecular ; Female ; Introns ; Male ; Molecular Sequence Data ; Mollusca/chemistry/*genetics/physiology ; Mucoproteins/chemistry/genetics/*metabolism ; Ovum/chemistry/physiology ; Receptors, Cell Surface/chemistry/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic ; Sequence Alignment ; Species Specificity ; Sperm-Ovum Interactions ; Spermatozoa/chemistry/physiology ; Vitelline Membrane/*chemistry/metabolism
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-09
    Description: A "switch" mutant of the Arc repressor homodimer was constructed by interchanging the sequence positions of a hydrophobic core residue, leucine 12, and an adjacent surface polar residue, asparagine 11, in each strand of an intersubunit beta sheet. The mutant protein adopts a fold in which each beta strand is replaced by a right-handed helix and side chains in this region undergo significant repacking. The observed structural changes allow the protein to maintain solvent exposure of polar side chains and optimal burial of hydrophobic side chains. These results suggest that new protein folds can evolve from existing folds without drastic or large-scale mutagenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cordes, M H -- Walsh, N P -- McKnight, C J -- Sauer, R T -- AI-15706/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):325-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, 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/10195898" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Asparagine/chemistry ; Circular Dichroism ; Hydrogen Bonding ; Leucine/chemistry ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Insertional ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; *Protein Folding ; *Protein Structure, Secondary ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry ; Viral Proteins/*chemistry ; Viral Regulatory and Accessory Proteins
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  • 30
    Publication Date: 1999-10-09
    Description: The Yersinia pseudotuberculosis invasin protein promotes bacterial entry by binding to host cell integrins with higher affinity than natural substrates such as fibronectin. The 2.3 angstrom crystal structure of the invasin extracellular region reveals five domains that form a 180 angstrom rod with structural similarities to tandem fibronectin type III domains. The integrin-binding surfaces of invasin and fibronectin include similarly located key residues, but in the context of different folds and surface shapes. The structures of invasin and fibronectin provide an example of convergent evolution, in which invasin presents an optimized surface for integrin binding, in comparison with host substrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamburger, Z A -- Brown, M S -- Isberg, R R -- Bjorkman, P J -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):291-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 156-29, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514372" target="_blank"〉PubMed〈/a〉
    Keywords: *Adhesins, Bacterial ; Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Evolution, Molecular ; Fibronectins/chemistry/metabolism ; Hydrogen Bonding ; Integrins/*metabolism ; Ligands ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Yersinia pseudotuberculosis/*chemistry/metabolism
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  • 31
    Publication Date: 1999-09-25
    Description: The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aramburu, J -- Yaffe, M B -- Lopez-Rodriguez, C -- Cantley, L C -- Hogan, P G -- Rao, A -- R01 AI 40127/AI/NIAID NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 HL 03601/HL/NHLBI NIH HHS/ -- R43 AI 43726/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2129-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10497131" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Calcineurin/*metabolism ; Calcineurin Inhibitors ; Cell Nucleus/metabolism ; Cyclosporine/pharmacology ; Cytokines/biosynthesis/genetics ; DNA-Binding Proteins/*antagonists & inhibitors/chemistry/metabolism ; Gene Expression Regulation ; Genes, Reporter ; HeLa Cells ; Humans ; Immunosuppressive Agents/chemistry/metabolism/*pharmacology ; Jurkat Cells ; Molecular Sequence Data ; NFATC Transcription Factors ; *Nuclear Proteins ; Oligopeptides/chemistry/metabolism/*pharmacology ; Peptide Library ; Peptides/chemistry/metabolism/*pharmacology ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes/*drug effects/immunology ; Transcription Factors/*antagonists & inhibitors/chemistry/metabolism ; Transfection
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  • 32
    Publication Date: 1999-11-05
    Description: The Brca1 (breast cancer gene 1) tumor suppressor protein is phosphorylated in response to DNA damage. Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation. ATM resides in a complex with Brca1 and phosphorylated Brca1 in vivo and in vitro in a region that contains clusters of serine-glutamine residues. Phosphorylation of this domain appears to be functionally important because a mutated Brca1 protein lacking two phosphorylation sites failed to rescue the radiation hypersensitivity of a Brca1-deficient cell line. Thus, phosphorylation of Brca1 by the checkpoint kinase ATM may be critical for proper responses to DNA double-strand breaks and may provide a molecular explanation for the role of ATM in breast cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cortez, D -- Wang, Y -- Qin, J -- Elledge, S J -- GM44664/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1162-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550055" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Ataxia Telangiectasia/genetics ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 Protein/*metabolism ; Breast Neoplasms/genetics ; Cell Cycle Proteins ; Cell Line ; *DNA Damage ; *DNA Repair ; DNA, Complementary ; DNA-Binding Proteins ; Female ; Gamma Rays ; Genes, BRCA1 ; Genetic Predisposition to Disease ; HeLa Cells ; Heterozygote ; Humans ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Tumor Suppressor Proteins
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  • 33
    Publication Date: 1999-10-03
    Description: Precursors of alpha-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT-/-) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT-/- mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT-/- mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, C L -- Ouellette, A J -- Satchell, D P -- Ayabe, T -- Lopez-Boado, Y S -- Stratman, J L -- Hultgren, S J -- Matrisian, L M -- Parks, W C -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):113-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson_c@kids.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10506557" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalysis ; Cytoplasmic Granules/enzymology ; Escherichia coli/growth & development ; Escherichia coli Infections/immunology/microbiology ; Female ; Humans ; *Immunity, Innate ; *Immunity, Mucosal ; Intestinal Mucosa/enzymology/immunology/microbiology ; Intestine, Small/enzymology/*immunology/microbiology ; Male ; Matrix Metalloproteinase 7 ; Metalloendopeptidases/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Paneth Cells/enzymology ; Protein Precursors/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Salmonella typhimurium/growth & development/pathogenicity ; Tissue Extracts/pharmacology
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-26
    Description: Katanin, a member of the AAA adenosine triphosphatase (ATPase) superfamily, uses nucleotide hydrolysis energy to sever and disassemble microtubules. Many AAA enzymes disassemble stable protein-protein complexes, but their mechanisms are not well understood. A fluorescence resonance energy transfer assay demonstrated that the p60 subunit of katanin oligomerized in an adenosine triphosphate (ATP)- and microtubule-dependent manner. Oligomerization increased the affinity of katanin for microtubules and stimulated its ATPase activity. After hydrolysis of ATP, microtubule-bound katanin oligomers disassembled microtubules and then dissociated into free katanin monomers. Coupling a nucleotide-dependent oligomerization cycle to the disassembly of a target protein complex may be a general feature of ATP-hydrolyzing AAA domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartman, J J -- Vale, R D -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):782-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, 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/10531065" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*chemistry/*metabolism ; Adenosine Triphosphate/analogs & derivatives/*metabolism ; Amino Acid Sequence ; Centrifugation, Density Gradient ; Fluorescence ; Hydrolysis ; Luminescent Proteins ; Microtubules/*metabolism ; Models, Biological ; Molecular Sequence Data ; Polymers ; Recombinant Fusion Proteins/chemistry/metabolism ; Tubulin/metabolism
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  • 35
    Publication Date: 1999-01-23
    Description: The plant hormone abscisic acid (ABA) regulates potassium and chloride ion channels at the plasma membrane of guard cells, leading to stomatal closure that reduces transpirational water loss from the leaf. The tobacco Nt-SYR1 gene encodes a syntaxin that is associated with the plasma membrane. Syntaxins and related SNARE proteins aid intracellular vesicle trafficking, fusion, and secretion. Disrupting Nt-Syr1 function by cleavage with Clostridium botulinum type C toxin or competition with a soluble fragment of Nt-Syr1 prevents potassium and chloride ion channel response to ABA in guard cells and implicates Nt-Syr1 in an ABA-signaling cascade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leyman, B -- Geelen, D -- Quintero, F J -- Blatt, M R -- New York, N.Y. -- Science. 1999 Jan 22;283(5401):537-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Plant Physiology and Biophysics, University of London, Wye College, Wye, Kent TN25 5AH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9915701" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*pharmacology ; Amino Acid Sequence ; Animals ; Botulinum Toxins/metabolism ; Cell Membrane/physiology ; Chloride Channels/*physiology ; Genes, Plant ; Genetic Complementation Test ; Ion Channel Gating/drug effects ; Membrane Proteins/chemistry/genetics/*physiology ; Molecular Sequence Data ; Oocytes ; Patch-Clamp Techniques ; Plant Growth Regulators/*pharmacology ; Plant Leaves/*physiology ; *Plants, Toxic ; Potassium Channels/*physiology ; Qa-SNARE Proteins ; Saccharomyces cerevisiae/genetics/growth & development ; Signal Transduction ; Tobacco/genetics/*physiology ; Xenopus
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  • 36
    Publication Date: 1999-11-05
    Description: Glutamatergic neurotransmission is controlled by presynaptic metabotropic glutamate receptors (mGluRs). A subdomain in the intracellular carboxyl-terminal tail of group III mGluRs binds calmodulin and heterotrimeric guanosine triphosphate-binding protein (G protein) betagamma subunits in a mutually exclusive manner. Mutations interfering with calmodulin binding and calmodulin antagonists inhibit G protein-mediated modulation of ionic currents by mGluR 7. Calmodulin antagonists also prevent inhibition of excitatory neurotransmission via presynaptic mGluRs. These results reveal a novel mechanism of presynaptic modulation in which Ca(2+)-calmodulin is required to release G protein betagamma subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, V -- El Far, O -- Bofill-Cardona, E -- Nanoff, C -- Freissmuth, M -- Karschin, A -- Airas, J M -- Betz, H -- Boehm, S -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1180-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550060" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Calmodulin/antagonists & inhibitors/*metabolism ; Cells, Cultured ; Dimerization ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; GTP-Binding Proteins/*metabolism ; Glutamic Acid/*metabolism ; Hippocampus/cytology/metabolism ; Humans ; Mice ; Molecular Sequence Data ; Neurons/metabolism ; Potassium Channels/metabolism ; *Potassium Channels, Inwardly Rectifying ; Presynaptic Terminals/metabolism ; Propionates/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/antagonists & inhibitors/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sesterterpenes ; Signal Transduction ; Swine ; *Synaptic Transmission ; Terpenes/pharmacology
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  • 37
    Publication Date: 1999-02-26
    Description: Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bachmaier, K -- Neu, N -- de la Maza, L M -- Pal, S -- Hessel, A -- Penninger, J M -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1335-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10037605" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Antigens, Bacterial/chemistry/immunology ; Autoantibodies/biosynthesis ; Autoimmune Diseases/immunology/*microbiology/pathology ; B-Lymphocytes/immunology ; Bacterial Outer Membrane Proteins/chemistry/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Chlamydia/*immunology ; Chlamydia Infections/complications/*immunology ; Chlamydia trachomatis/immunology ; CpG Islands ; Humans ; Immunization ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; *Molecular Mimicry ; Molecular Sequence Data ; Myocarditis/immunology/*microbiology/pathology ; Myocardium/immunology/pathology ; Myosin Heavy Chains/chemistry/*immunology ; Oligodeoxyribonucleotides/immunology ; Sequence Homology, Amino Acid
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-19
    Description: A single kinesin molecule can move "processively" along a microtubule for more than 1 micrometer before detaching from it. The prevailing explanation for this processive movement is the "walking model," which envisions that each of two motor domains (heads) of the kinesin molecule binds coordinately to the microtubule. This implies that each kinesin molecule must have two heads to "walk" and that a single-headed kinesin could not move processively. Here, a motor-domain construct of KIF1A, a single-headed kinesin superfamily protein, was shown to move processively along the microtubule for more than 1 micrometer. The movement along the microtubules was stochastic and fitted a biased Brownian-movement model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Y -- Hirokawa, N -- New York, N.Y. -- Science. 1999 Feb 19;283(5405):1152-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10024239" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Catalytic Domain ; Diffusion ; Drosophila ; Kinesin/chemistry/*metabolism ; Kinetics ; Microscopy, Fluorescence ; Microtubules/*metabolism ; Models, Chemical ; Molecular Motor Proteins/chemistry/*metabolism ; Molecular Sequence Data ; Nerve Tissue Proteins/chemistry/*metabolism ; Recombinant Fusion Proteins ; Stochastic Processes ; Thermodynamics
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  • 39
    Publication Date: 1999-07-31
    Description: Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, J -- Song, Y -- Bakker, A B -- Bauer, S -- Spies, T -- Lanier, L L -- Phillips, J H -- AI30581/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):730-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10426994" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Line ; Cytotoxicity, Immunologic ; Humans ; Killer Cells, Natural/*immunology/metabolism ; Ligands ; *Lymphocyte Activation ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; NK Cell Lectin-Like Receptor Subfamily K ; Neoplasms/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Receptors, Immunologic/chemistry/genetics/*metabolism ; Receptors, Natural Killer Cell ; Signal Transduction ; T-Lymphocytes/*immunology/metabolism ; Tumor Cells, Cultured ; src Homology Domains
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sikorski, R -- Peters, R -- New York, N.Y. -- Science. 1999 Sep 17;285(5435):1868.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10515792" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Genetic Techniques ; Protein Binding ; Proteins/*isolation & purification/metabolism ; Recombinant Fusion Proteins/metabolism ; Ribonucleoproteins, Small Nuclear/metabolism ; Saccharomyces cerevisiae ; Sequence Analysis/*methods
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  • 41
    Publication Date: 2000-01-05
    Description: Phytochromes are a family of photoreceptors used by green plants to entrain their development to the light environment. The distribution of these chromoproteins has been expanded beyond photoautotrophs with the discovery of phytochrome-like proteins in the nonphotosynthetic eubacteria Deinococcus radiodurans and Pseudomonas aeruginosa. Like plant phytochromes, the D. radiodurans receptor covalently binds linear tetrapyrroles autocatalytically to generate a photochromic holoprotein. However, the attachment site is distinct, using a histidine to potentially form a Schiff base linkage. Sequence homology and mutational analysis suggest that D. radiodurans bacteriophytochrome functions as a light-regulated histidine kinase, which helps protect the bacterium from visible light.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S J -- Vener, A V -- Vierstra, R D -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2517-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, Cellular and Molecular Biology Program and Department of Horticulture, University of Wisconsin-Madison, 1575 Linden Drive, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617469" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biliverdine/analogs & derivatives/metabolism ; Binding Sites ; Gram-Positive Cocci/genetics/*metabolism ; Histidine/metabolism ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Photoreceptors, Microbial/chemistry/genetics/*metabolism ; Phytochrome/metabolism ; Protein Kinases/chemistry/genetics/*metabolism ; Pseudomonas aeruginosa/*metabolism ; Signal Transduction
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  • 42
    Publication Date: 1999-04-09
    Description: Mature Arabidopsis seeds are enriched in storage proteins and lipids, but lack starch. In the shrunken seed 1 (sse1) mutant, however, starch is favored over proteins and lipids as the major storage compound. SSE1 has 26 percent identity with Pex16p in Yarrowia lipolytica and complements pex16 mutants defective in the formation of peroxisomes and the transportation of plasma membrane- and cell wall-associated proteins. In Arabidopsis maturing seeds, SSE1 is required for protein and oil body biogenesis, both of which are endoplasmic reticulum-dependent. Starch accumulation in sse1 suggests that starch formation is a default storage deposition pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Y -- Sun, L -- Nguyen, L V -- Rachubinski, R A -- Goodman, H M -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):328-30.〈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/10195899" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*metabolism/ultrastructure ; *Arabidopsis Proteins ; *Fungal Proteins ; Gene Expression ; Genetic Complementation Test ; Membrane Proteins/chemistry/genetics ; Microbodies/metabolism/ultrastructure ; Microscopy, Electron ; Molecular Sequence Data ; Mutation ; Organelles/*metabolism/ultrastructure ; Phenotype ; Plant Oils/metabolism ; Plant Proteins/chemistry/genetics/metabolism/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomycetales/chemistry/genetics/metabolism ; Seeds/*metabolism/ultrastructure ; Starch/metabolism
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  • 43
    Publication Date: 1999-01-05
    Description: CmPP16 from Cucurbita maxima was cloned and the protein was shown to possess properties similar to those of viral movement proteins. CmPP16 messenger RNA (mRNA) is present in phloem tissue, whereas protein appears confined to sieve elements (SE). Microinjection and grafting studies revealed that CmPP16 moves from cell to cell, mediates the transport of sense and antisense RNA, and moves together with its mRNA into the SE of scion tissue. CmPP16 possesses the characteristics that are likely required to mediate RNA delivery into the long-distance translocation stream. Thus, RNA may move within the phloem as a component of a plant information superhighway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xoconostle-Cazares, B -- Xiang, Y -- Ruiz-Medrano, R -- Wang, H L -- Monzer, J -- Yoo, B C -- McFarland, K C -- Franceschi, V R -- Lucas, W J -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):94-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Plant Biology, Division of Biological Sciences, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9872750" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Transport ; Cloning, Molecular ; Cucumis sativus ; Cucurbitaceae/genetics/*metabolism ; Microinjections ; Molecular Sequence Data ; Plant Leaves/metabolism ; Plant Proteins/chemistry/genetics/*metabolism ; Plant Roots/metabolism ; Plant Stems/metabolism ; Plant Viral Movement Proteins ; RNA, Antisense/metabolism ; RNA, Messenger/*metabolism ; RNA, Plant/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Viral Proteins/chemistry/metabolism
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  • 44
    Publication Date: 1999-07-03
    Description: Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon, D B -- Lu, Y -- Choate, K A -- Velazquez, H -- Al-Sabban, E -- Praga, M -- Casari, G -- Bettinelli, A -- Colussi, G -- Rodriguez-Soriano, J -- McCredie, D -- Milford, D -- Sanjad, S -- Lifton, R P -- F.1/Telethon/Italy -- R01DK51696/DK/NIDDK NIH HHS/ -- TGM06S01/Telethon/Italy -- New York, N.Y. -- Science. 1999 Jul 2;285(5424):103-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10390358" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calcium/urine ; Chromosomes, Human, Pair 3/genetics ; Claudins ; Cloning, Molecular ; Female ; Genes, Recessive ; Homeostasis ; Humans ; Kidney Diseases/*genetics/metabolism ; Kidney Tubules/chemistry ; Loop of Henle/chemistry/*metabolism ; Magnesium/blood/*metabolism ; Magnesium Deficiency/*genetics/metabolism ; Male ; Membrane Proteins/analysis/chemistry/genetics/*physiology ; Molecular Sequence Data ; Mutation ; Pedigree ; Physical Chromosome Mapping ; Tight Junctions/*metabolism
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  • 45
    Publication Date: 1999-04-09
    Description: IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK) phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation loop of IKKbeta was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delhase, M -- Hayakawa, M -- Chen, Y -- Karin, M -- R01 AI43477/AI/NIAID NIH HHS/ -- R37 ES04151/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):309-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195894" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Cell Line ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; HeLa Cells ; Helix-Loop-Helix Motifs ; Humans ; I-kappa B Kinase ; I-kappa B Proteins ; Interleukin-1/pharmacology ; Leucine Zippers ; *MAP Kinase Kinase Kinase 1 ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Phosphoserine/metabolism ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Transfection ; Tumor Necrosis Factor-alpha/pharmacology
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  • 46
    Publication Date: 1999-04-16
    Description: Mutation of the VHL tumor suppressor is associated with the inherited von Hippel-Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ElonginC-ElonginB complex and regulates levels of hypoxia-inducible proteins. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ElonginC and another between ElonginC and ElonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ElonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stebbins, C E -- Kaelin, W G Jr -- Pavletich, N P -- New York, N.Y. -- Science. 1999 Apr 16;284(5413):455-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Structural Biology, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10205047" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cell Cycle Proteins/chemistry/metabolism ; Cloning, Molecular ; Crystallography, X-Ray ; *Genes, Tumor Suppressor ; Humans ; Hydrogen Bonding ; *Ligases ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Neoplasms/genetics ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Proteins/*chemistry/genetics/metabolism ; S-Phase Kinase-Associated Proteins ; Surface Properties ; Transcription Factors/*chemistry/metabolism ; *Tumor Suppressor Proteins ; *Ubiquitin-Protein Ligases ; Von Hippel-Lindau Tumor Suppressor Protein ; von Hippel-Lindau Disease/*genetics
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  • 47
    Publication Date: 1999-10-09
    Description: Norwalk virus, a noncultivatable human calicivirus, is the major cause of epidemic gastroenteritis in humans. The first x-ray structure of a calicivirus capsid, which consists of 180 copies of a single protein, has been determined by phase extension from a low-resolution electron microscopy structure. The capsid protein has a protruding (P) domain connected by a flexible hinge to a shell (S) domain that has a classical eight-stranded beta-sandwich motif. The structure of the P domain is unlike that of any other viral protein with a subdomain exhibiting a fold similar to that of the second domain in the eukaryotic translation elongation factor-Tu. This subdomain, located at the exterior of the capsid, has the largest sequence variation among Norwalk-like human caliciviruses and is likely to contain the determinants of strain specificity and cell binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prasad, B V -- Hardy, M E -- Dokland, T -- Bella, J -- Rossmann, M G -- Estes, M K -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):287-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Marrs Mclean Department of Biochemistry, Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA. bprasad@bcm.tmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514371" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Capsid/*chemistry/metabolism ; *Capsid Proteins ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Dimerization ; Genome, Viral ; Humans ; Hydrogen Bonding ; Image Processing, Computer-Assisted ; Models, Molecular ; Molecular Sequence Data ; Norwalk virus/*chemistry/genetics/physiology ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Recombinant Proteins/chemistry ; Virus Assembly
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  • 48
    Publication Date: 1999-10-09
    Description: Ubiquitination of receptor protein-tyrosine kinases (RPTKs) terminates signaling by marking active receptors for degradation. c-Cbl, an adapter protein for RPTKs, positively regulates RPTK ubiquitination in a manner dependent on its variant SRC homology 2 (SH2) and RING finger domains. Ubiquitin-protein ligases (or E3s) are the components of ubiquitination pathways that recognize target substrates and promote their ligation to ubiquitin. The c-Cbl protein acted as an E3 that can recognize tyrosine-phosphorylated substrates, such as the activated platelet-derived growth factor receptor, through its SH2 domain and that recruits and allosterically activates an E2 ubiquitin-conjugating enzyme through its RING domain. These results reveal an SH2-containing protein that functions as a ubiquitin-protein ligase and thus provide a distinct mechanism for substrate targeting in the ubiquitin system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joazeiro, C A -- Wing, S S -- Huang, H -- Leverson, J D -- Hunter, T -- Liu, Y C -- CA39780/CA/NCI NIH HHS/ -- R01 DK56558/DK/NIDDK NIH HHS/ -- T32CA09523/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):309-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514377" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Humans ; Ligases/chemistry/*metabolism ; Molecular Sequence Data ; Phosphotyrosine/metabolism ; Point Mutation ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-cbl ; Receptor Protein-Tyrosine Kinases/*metabolism ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; Signal Transduction ; *Ubiquitin-Conjugating Enzymes ; Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism ; src Homology Domains
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  • 49
    Publication Date: 1999-03-19
    Description: In higher plants, organogenesis occurs continuously from self-renewing apical meristems. Arabidopsis thaliana plants with loss-of-function mutations in the CLAVATA (CLV1, 2, and 3) genes have enlarged meristems and generate extra floral organs. Genetic analysis indicates that CLV1, which encodes a receptor kinase, acts with CLV3 to control the balance between meristem cell proliferation and differentiation. CLV3 encodes a small, predicted extracellular protein. CLV3 acts nonautonomously in meristems and is expressed at the meristem surface overlying the CLV1 domain. These proteins may act as a ligand-receptor pair in a signal transduction pathway, coordinating growth between adjacent meristematic regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fletcher, J C -- Brand, U -- Running, M P -- Simon, R -- Meyerowitz, E M -- New York, N.Y. -- Science. 1999 Mar 19;283(5409):1911-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10082464" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/*cytology/genetics/growth & development/metabolism ; *Arabidopsis Proteins ; Cell Differentiation ; Cell Division ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genes, Plant ; In Situ Hybridization ; Ligands ; Meristem/*cytology/growth & development/metabolism ; Molecular Sequence Data ; Mutation ; Phenotype ; Plant Proteins/chemistry/genetics/*metabolism ; Plant Shoots/cytology ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction
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  • 50
    Publication Date: 1999-07-10
    Description: Drug resistance of pathogens is an increasing problem whose underlying mechanisms are not fully understood. Cellular uptake of the major drugs against Trypanosoma brucei spp., the causative agents of sleeping sickness, is thought to occur through an unusual, so far unidentified adenosine transporter. Saccharomyces cerevisiae was used in a functional screen to clone a gene (TbAT1) from Trypanosoma brucei brucei that encodes a nucleoside transporter. When expressed in yeast, TbAT1 enabled adenosine uptake and conferred susceptibility to melaminophenyl arsenicals. Drug-resistant trypanosomes harbor a defective TbAT1 variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maser, P -- Sutterlin, C -- Kralli, A -- Kaminsky, R -- New York, N.Y. -- Science. 1999 Jul 9;285(5425):242-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Tropical Institute, CH-4002 Basel, Switzerland. Biozentrum, University of Basel, CH-4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10398598" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*metabolism ; Amino Acid Sequence ; Animals ; Arsenicals/metabolism/pharmacology ; Biological Transport ; Carrier Proteins/chemistry/genetics/*metabolism ; Cloning, Molecular ; Drug Resistance/genetics ; Genes, Protozoan ; Membrane Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Nucleoside Transport Proteins ; Nucleosides/metabolism ; Purines/metabolism/pharmacology ; Saccharomyces cerevisiae/genetics ; Substrate Specificity ; Trypanocidal Agents/metabolism/*pharmacology ; Trypanosoma brucei brucei/*drug effects/genetics/*metabolism ; Trypanosomiasis, African/drug therapy/parasitology
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  • 51
    Publication Date: 1999-10-16
    Description: Analysis of rhesus macaque leukocytes disclosed the presence of an 18-residue macrocyclic, tridisulfide antibiotic peptide in granules of neutrophils and monocytes. The peptide, termed rhesus theta defensin-1 (RTD-1), is microbicidal for bacteria and fungi at low micromolar concentrations. Antibacterial activity of the cyclic peptide was threefold greater than that of an open-chain analog, and the cyclic conformation was required for antimicrobial activity in the presence of 150 millimolar sodium chloride. Biosynthesis of RTD-1 involves the head-to-tail ligation of two alpha-defensin-related nonapeptides, requiring the formation of two new peptide bonds. Thus, host defense cells possess mechanisms for synthesis and granular packaging of macrocyclic antibiotic peptides that are components of the phagocyte antimicrobial armamentarium.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Y Q -- Yuan, J -- Osapay, G -- Osapay, K -- Tran, D -- Miller, C J -- Ouellette, A J -- Selsted, M E -- AI22931/AI/NIAID NIH HHS/ -- DK33506/DK/NIDDK NIH HHS/ -- DK44632/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):498-502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, College of Medicine, University of California, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521339" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Bacterial Agents ; Anti-Infective Agents/chemistry/*metabolism/pharmacology ; Bacteria/drug effects ; Cloning, Molecular ; Defensins ; Disulfides/chemistry ; Fungi/drug effects ; Humans ; Leukopoiesis ; Macaca mulatta ; Molecular Sequence Data ; Monocytes/*metabolism ; Neutrophils/*metabolism ; Oligopeptides/chemistry/genetics/metabolism ; Osmolar Concentration ; Peptides, Cyclic/*biosynthesis/chemistry/genetics/pharmacology ; *Protein Biosynthesis ; Protein Conformation ; Protein Precursors/chemistry/genetics/metabolism ; Protein Processing, Post-Translational ; Proteins/chemistry/genetics/pharmacology
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1247, 1249.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10084927" target="_blank"〉PubMed〈/a〉
    Keywords: 14-3-3 Proteins ; Amino Acid Sequence ; Cell Cycle Proteins/metabolism ; Cell Nucleus/metabolism ; *Conserved Sequence ; Mitosis ; Peptidylprolyl Isomerase/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphoproteins/chemistry/*metabolism ; Phosphorylation ; Phosphoserine/*metabolism ; Phosphotyrosine/metabolism ; Protein Binding ; Proteins/*chemistry/*metabolism ; *Tyrosine 3-Monooxygenase ; cdc25 Phosphatases
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  • 53
    Publication Date: 2000-09-01
    Description: Activation of the transcription factor nuclear factor (NF)-kappaB by proinflammatory stimuli leads to increased expression of genes involved in inflammation. Activation of NF-kappaB requires the activity of an inhibitor of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier). An amino-terminal alpha-helical region of NEMO associated with a carboxyl-terminal segment of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell-permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine-induced NF-kappaB activation and NF-kappaB-dependent gene expression. The peptide also ameliorated inflammatory responses in two experimental mouse models of acute inflammation. The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉May, M J -- D'Acquisto, F -- Madge, L A -- Glockner, J -- Pober, J S -- Ghosh, S -- AI 33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1550-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968790" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/pharmacology ; COS Cells ; Cells, Cultured ; E-Selectin/biosynthesis/genetics ; Endothelium, Vascular/metabolism ; Gene Expression Regulation ; HeLa Cells ; Humans ; I-kappa B Kinase ; Inflammation/drug therapy ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; NF-kappa B/*metabolism ; Peptides/chemistry/*pharmacology ; Point Mutation ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism
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  • 54
    Publication Date: 2000-03-04
    Description: The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in Xenopus laevis oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plugge, B -- Gazzarrini, S -- Nelson, M -- Cerana, R -- Van Etten, J L -- Derst, C -- DiFrancesco, D -- Moroni, A -- Thiel, G -- 971/Telethon/Italy -- GM32441/GM/NIGMS NIH HHS/ -- GM41333/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Mar 3;287(5458):1641-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Albrecht-von-Haller-Institut fur Pflanzenwissenschaften, Universitat Gottingen, 37073 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10698737" target="_blank"〉PubMed〈/a〉
    Keywords: Amantadine/pharmacology ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Barium/pharmacology ; Cesium/pharmacology ; Chlorella/virology ; Isoelectric Point ; Molecular Sequence Data ; Molecular Weight ; Oocytes ; Patch-Clamp Techniques ; Phycodnaviridae/chemistry/drug effects/*genetics/*physiology ; Potassium/metabolism ; Potassium Channels/*chemistry/genetics/*physiology ; RNA, Messenger/genetics/metabolism ; Recombinant Proteins/metabolism ; Sodium/metabolism ; Viral Plaque Assay ; *Viral Proteins ; Virus Replication/drug effects ; Xenopus laevis
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  • 55
    Publication Date: 1999-12-30
    Description: The Smad proteins mediate transforming growth factor-beta (TGFbeta) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFbeta receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2 angstrom resolution. SARA SBD, in an extended conformation comprising a rigid coil, an alpha helix, and a beta strand, interacts with the beta sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 beta sheet is essential for specificity, whereas interactions between the SARA beta strand and the Smad2 three-helix bundle contribute significantly to binding affinity. Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, G -- Chen, Y G -- Ozdamar, B -- Gyuricza, C A -- Chong, P A -- Wrana, J L -- Massague, J -- Shi, Y -- CA85171/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 7;287(5450):92-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10615055" target="_blank"〉PubMed〈/a〉
    Keywords: *Activin Receptors, Type I ; Amino Acid Sequence ; Binding Sites ; Carrier Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; DNA-Binding Proteins/*chemistry/genetics/*metabolism ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Point Mutation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/metabolism ; Receptors, Transforming Growth Factor beta/chemistry/genetics/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Signal Transduction ; Smad2 Protein ; Trans-Activators/*chemistry/genetics/*metabolism ; Zinc Fingers
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  • 56
    Publication Date: 2000-10-20
    Description: Ectodysplasin, a member of the tumor necrosis factor family, is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Mutations in EDA give rise to a clinical syndrome characterized by loss of hair, sweat glands, and teeth. EDA-A1 and EDA-A2 are two isoforms of ectodysplasin that differ only by an insertion of two amino acids. This insertion functions to determine receptor binding specificity, such that EDA-A1 binds only the receptor EDAR, whereas EDA-A2 binds only the related, but distinct, X-linked ectodysplasin-A2 receptor (XEDAR). In situ binding and organ culture studies indicate that EDA-A1 and EDA-A2 are differentially expressed and play a role in epidermal morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, M -- Wang, L C -- Hymowitz, S G -- Schilbach, S -- Lee, J -- Goddard, A -- de Vos, A M -- Gao, W Q -- Dixit, V M -- New York, N.Y. -- Science. 2000 Oct 20;290(5491):523-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11039935" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Binding Sites ; Cell Line ; DNA-Binding Proteins/metabolism ; Ectodermal Dysplasia/genetics ; Ectodysplasins ; Epidermis/embryology/*metabolism ; Humans ; *I-kappa B Proteins ; In Situ Hybridization ; Ligands ; Membrane Proteins/*chemistry/*metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Morphogenesis ; NF-kappa B/metabolism ; Phosphorylation ; Point Mutation ; Protein Conformation ; Proteins/metabolism ; Receptors, Cell Surface/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; TNF Receptor-Associated Factor 6 ; Transfection
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-10
    Description: A Drosophila model for Huntington's and other polyglutamine diseases was used to screen for genetic factors modifying the degeneration caused by expression of polyglutamine in the eye. Among 7000 P-element insertions, several suppressor strains were isolated, two of which led to the discovery of the suppressor genes described here. The predicted product of one, dHDJ1, is homologous to human heat shock protein 40/HDJ1. That of the second, dTPR2, is homologous to the human tetratricopeptide repeat protein 2. Each of these molecules contains a chaperone-related J domain. Their suppression of polyglutamine toxicity was verified in transgenic flies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kazemi-Esfarjani, P -- Benzer, S -- New York, N.Y. -- Science. 2000 Mar 10;287(5459):1837-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. parsa@its.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10710314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Cloning, Molecular ; Crosses, Genetic ; DNA Transposable Elements ; Disease Models, Animal ; *Drosophila Proteins ; Drosophila melanogaster/anatomy & histology/embryology/*genetics/metabolism ; Expressed Sequence Tags ; Eye/metabolism ; Eye Abnormalities ; Female ; Genes, Insect ; *Genes, Suppressor ; HSP40 Heat-Shock Proteins ; Heat-Shock Proteins/chemistry/*genetics/physiology ; Male ; Molecular Sequence Data ; *Nerve Degeneration ; Neurodegenerative Diseases ; Peptides/genetics/*metabolism ; Phenotype ; Proteins/chemistry ; Repetitive Sequences, Nucleic Acid ; Retina/metabolism ; Suppression, Genetic
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  • 58
    Publication Date: 2000-02-11
    Description: The nonclassical major histocompatibility complex (MHC) class I molecule HLA-E inhibits natural killer (NK) cell-mediated lysis by interacting with CD94/NKG2A receptors. Surface expression of HLA-E depends on binding of conserved peptides derived from MHC class I molecules. The same peptide is present in the leader sequence of the human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It is shown that, independently of the transporter associated with antigen processing, gpUL40 can up-regulate expression of HLA-E, which protects targets from NK cell lysis. While classical MHC class I molecules are down-regulated, HLA-E is up-regulated by HCMV. Induction of HLA-E surface expression by gpUL40 may represent an escape route for HCMV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomasec, P -- Braud, V M -- Rickards, C -- Powell, M B -- McSharry, B P -- Gadola, S -- Cerundolo, V -- Borysiewicz, L K -- McMichael, A J -- Wilkinson, G W -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1031.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Wales College of Medicine, Cardiff CF14 4XN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669413" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; *Antigens, CD ; Cell Line ; Cell Membrane/immunology ; Cells, Cultured ; Conserved Sequence ; Cytomegalovirus/genetics/immunology/*metabolism ; Cytotoxicity, Immunologic ; Down-Regulation ; HLA Antigens/immunology/*metabolism ; Histocompatibility Antigens Class I/immunology/*metabolism ; Humans ; Killer Cells, Natural/*immunology ; Molecular Sequence Data ; Open Reading Frames ; Protein Sorting Signals/chemistry/*metabolism ; Receptors, Immunologic/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Transfection ; Up-Regulation ; Viral Proteins/chemistry/genetics/*metabolism
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  • 59
    Publication Date: 2000-04-25
    Description: Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position beta57. I-Ag7 lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-Ag7 was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-Ag7 has a substantially wider peptide-binding groove around beta57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp(beta57) leads to an oxyanion hole in I-Ag7 that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corper, A L -- Stratmann, T -- Apostolopoulos, V -- Scott, C A -- Garcia, K C -- Kang, A S -- Wilson, I A -- Teyton, L -- CA58896/CA/NCI NIH HHS/ -- DK55037/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):505-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Skaggs Institute for Chemical 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/10775108" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Aspartic Acid/chemistry ; Crystallography, X-Ray ; Diabetes Mellitus, Type 1/*immunology ; Drosophila melanogaster ; *Genes, MHC Class II ; Glutamate Decarboxylase/metabolism ; Histocompatibility Antigens Class II/*chemistry/genetics/metabolism ; Humans ; Hydrogen Bonding ; Mice ; Mice, Inbred NOD ; Models, Molecular ; Molecular Sequence Data ; Peptide Library ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell/metabolism ; Recombinant Proteins/chemistry/metabolism
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-31
    Description: All cellular organisms use specialized RNA polymerases called "primases" to synthesize RNA primers for the initiation of DNA replication. The high-resolution crystal structure of a primase, comprising the catalytic core of the Escherichia coli DnaG protein, was determined. The core structure contains an active-site architecture that is unrelated to other DNA or RNA polymerase palm folds, but is instead related to the "toprim" fold. On the basis of the structure, it is likely that DnaG binds nucleic acid in a groove clustered with invariant residues and that DnaG is positioned within the replisome to accept single-stranded DNA directly from the replicative helicase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keck, J L -- Roche, D D -- Lynch, A S -- Berger, J M -- New York, N.Y. -- Science. 2000 Mar 31;287(5462):2482-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall, no. 3206, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10741967" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; DNA Helicases/chemistry/metabolism ; DNA Primase/*chemistry/*metabolism ; DNA Replication ; DNA, Bacterial/metabolism ; DNA, Single-Stranded/*metabolism ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Escherichia coli/*enzymology/metabolism ; Metals/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/biosynthesis ; Recombinant Proteins/chemistry/metabolism ; Templates, Genetic
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  • 61
    Publication Date: 2000-08-05
    Description: The circadian oscillator of the cyanobacterium Synechococcus elongatus, like those in eukaryotes, is entrained by environmental cues. Inactivation of the gene cikA (circadian input kinase) shortens the circadian period of gene expression rhythms in S. elongatus by approximately 2 hours, changes the phasing of a subset of rhythms, and nearly abolishes resetting of phase by a pulse of darkness. The CikA protein sequence reveals that it is a divergent bacteriophytochrome with characteristic histidine protein kinase motifs and a cryptic response regulator motif. CikA is likely a key component of a pathway that provides environmental input to the circadian oscillator in S. elongatus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmitz, O -- Katayama, M -- Williams, S B -- Kondo, T -- Golden, S S -- GM37040/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 4;289(5480):765-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10926536" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; *Bacterial Proteins ; *Biological Clocks/genetics/physiology ; *Circadian Rhythm/genetics/physiology ; Cyanobacteria/genetics/*physiology ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genes, Reporter ; Luminescent Measurements ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Kinases/chemistry/*genetics/physiology ; Sequence Alignment
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  • 62
    Publication Date: 2001-02-07
    Description: Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum. Individual bacteriorhodopsin molecules were first localized and then extracted from the membrane; the remaining vacancies were imaged again. Anchoring forces between 100 and 200 piconewtons for the different helices were found. Upon extraction, the helices were found to unfold. The force spectra revealed the individuality of the unfolding pathways. Helices G and F as well as helices E and D always unfolded pairwise, whereas helices B and C occasionally unfolded one after the other. Experiments with cleaved loops revealed the origin of the individuality: stabilization of helix B by neighboring helices.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oesterhelt, F -- Oesterhelt, D -- Pfeiffer, M -- Engel, A -- Gaub, H E -- Muller, D J -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):143-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CeNS and Lehrstuhl fur angewandte Physik, Ludwig Maximilians-Universitat Munchen, Amalienstrasse 54, 80799 Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10753119" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriorhodopsins/*chemistry/genetics ; Cysteine/chemistry ; Halobacterium salinarum/*chemistry ; Membrane Proteins/*chemistry/genetics ; *Microscopy, Atomic Force ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Denaturation ; *Protein Folding ; Protein Structure, Secondary ; Purple Membrane/*chemistry ; Serine Endopeptidases/metabolism ; Spectrum Analysis
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  • 63
    Publication Date: 2000-02-26
    Description: The signal recognition particle (SRP), a protein-RNA complex conserved in all three kingdoms of life, recognizes and transports specific proteins to cellular membranes for insertion or secretion. We describe here the 1.8 angstrom crystal structure of the universal core of the SRP, revealing protein recognition of a distorted RNA minor groove. Nucleotide analog interference mapping demonstrates the biological importance of observed interactions, and genetic results show that this core is functional in vivo. The structure explains why the conserved residues in the protein and RNA are required for SRP assembly and defines a signal sequence recognition surface composed of both protein and RNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Batey, R T -- Rambo, R P -- Lucast, L -- Rha, B -- Doudna, J A -- New York, N.Y. -- Science. 2000 Feb 18;287(5456):1232-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, CT 06511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10678824" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Base Pairing ; Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Escherichia coli/chemistry/genetics/metabolism ; *Escherichia coli Proteins ; Guanosine Triphosphate/metabolism ; Hydrogen Bonding ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Potassium/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Bacterial/*chemistry/genetics/metabolism ; Signal Recognition Particle/*chemistry/metabolism ; Transformation, Bacterial ; Water/metabolism
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-29
    Description: Evidence of simian immunodeficiency virus (SIV) infection has been reported for 26 different species of African nonhuman primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, are the cause of acquired immunodeficiency syndrome (AIDS) in humans. Together, they have been transmitted to humans on at least seven occasions. The implications of human infection by a diverse set of SIVs and of exposure to a plethora of additional human immunodeficiency virus-related viruses are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hahn, B H -- Shaw, G M -- De Cock, K M -- Sharp, P M -- N01 AI 35338/AI/NIAID NIH HHS/ -- R01 AI 40951/AI/NIAID NIH HHS/ -- R01 AI 44596/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):607-14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA. bhahn@uab.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10649986" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/epidemiology/*transmission/virology ; Africa, Western/epidemiology ; Amino Acid Sequence ; Animals ; Disease Outbreaks ; Disease Reservoirs ; *HIV-1/genetics ; *HIV-2/genetics ; Haplorhini/*virology ; Humans ; Molecular Sequence Data ; Phylogeny ; Public Health ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Immunodeficiency Virus/classification/genetics/*physiology ; Species Specificity ; Zoonoses/*transmission
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  • 65
    Publication Date: 2000-09-16
    Description: Extremely halophilic archaea contain retinal-binding integral membrane proteins called bacteriorhodopsins that function as light-driven proton pumps. So far, bacteriorhodopsins capable of generating a chemiosmotic membrane potential in response to light have been demonstrated only in halophilic archaea. We describe here a type of rhodopsin derived from bacteria that was discovered through genomic analyses of naturally occuring marine bacterioplankton. The bacterial rhodopsin was encoded in the genome of an uncultivated gamma-proteobacterium and shared highest amino acid sequence similarity with archaeal rhodopsins. The protein was functionally expressed in Escherichia coli and bound retinal to form an active, light-driven proton pump. The new rhodopsin exhibited a photochemical reaction cycle with intermediates and kinetics characteristic of archaeal proton-pumping rhodopsins. Our results demonstrate that archaeal-like rhodopsins are broadly distributed among different taxa, including members of the domain Bacteria. Our data also indicate that a previously unsuspected mode of bacterially mediated light-driven energy generation may commonly occur in oceanic surface waters worldwide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beja, O -- Aravind, L -- Koonin, E V -- Suzuki, M T -- Hadd, A -- Nguyen, L P -- Jovanovich, S B -- Gates, C M -- Feldman, R A -- Spudich, J L -- Spudich, E N -- DeLong, E F -- HG01775-02S1/HG/NHGRI NIH HHS/ -- R01GM27750/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 15;289(5486):1902-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Monterey Bay Aquarium Research Institute, Moss Landing, CA 95039-0628, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10988064" target="_blank"〉PubMed〈/a〉
    Keywords: Aerobiosis ; Amino Acid Sequence ; Archaea/classification/physiology ; Bacteria/genetics ; *Bacterial Physiological Phenomena ; Cloning, Molecular ; Escherichia coli ; Gammaproteobacteria/classification/genetics/*physiology ; Molecular Sequence Data ; Oceans and Seas ; Photochemistry ; Photosynthesis ; Phylogeny ; Phytoplankton/genetics/physiology ; Protein Binding ; Proton Pumps/physiology ; Retinaldehyde/metabolism ; Rhodopsin/*physiology ; Rhodopsins, Microbial ; *Water Microbiology
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 2000 Mar 17;287(5460):1954-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10755949" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biotechnology ; Computer Simulation ; Crystallography, X-Ray ; *Drug Design ; Humans ; Models, Molecular ; Private Sector ; *Protein Conformation ; Protein Folding ; Proteins/*chemistry/*genetics/physiology ; Proteome ; Public Sector ; Research Support as Topic
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  • 67
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-02-26
    Description: Spider flagelliform silk is one of the most elastic natural materials known. Extensive sequencing of spider silk genes has shown that the exons and introns of the flagelliform gene underwent intragenic concerted evolution. The intron sequences are more homogenized within a species than are the exons. This pattern can be explained by extreme mutation and recombination pressures on the internally repetitive exons. The iterated sequences within exons encode protein structures that are critical to the function of silks. Therefore, attributes that make silks exceptional biomaterials may also hinder the fixation of optimally adapted protein sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, C Y -- Lewis, R V -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1477-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Wyoming, Laramie, WY 82071-3944, USA. hayashi@uwyo.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10688794" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Crossing Over, Genetic ; DNA/genetics ; DNA Replication ; *Evolution, Molecular ; *Exons ; Gene Conversion ; *Genes ; *Introns ; Molecular Sequence Data ; Mutation ; Proteins/chemistry/*genetics ; Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic ; Species Specificity ; Spiders/*genetics
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  • 68
    Publication Date: 2001-04-21
    Description: Structures of a 10-subunit yeast RNA polymerase II have been derived from two crystal forms at 2.8 and 3.1 angstrom resolution. Comparison of the structures reveals a division of the polymerase into four mobile modules, including a clamp, shown previously to swing over the active center. In the 2.8 angstrom structure, the clamp is in an open state, allowing entry of straight promoter DNA for the initiation of transcription. Three loops extending from the clamp may play roles in RNA unwinding and DNA rewinding during transcription. A 2.8 angstrom difference Fourier map reveals two metal ions at the active site, one persistently bound and the other possibly exchangeable during RNA synthesis. The results also provide evidence for RNA exit in the vicinity of the carboxyl-terminal repeat domain, coupling synthesis to RNA processing by enzymes bound to this domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cramer, P -- Bushnell, D A -- Kornberg, R D -- GM49985/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1863-76. Epub 2001 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11313498" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Conserved Sequence ; Crystallography, X-Ray ; DNA, Fungal/chemistry/metabolism ; Fourier Analysis ; Hydrogen Bonding ; Magnesium/metabolism ; Metals/metabolism ; Models, Molecular ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits ; RNA Polymerase II/*chemistry/*metabolism ; RNA Processing, Post-Transcriptional ; RNA, Fungal/biosynthesis/chemistry/metabolism ; RNA, Messenger/biosynthesis/chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Transcription Factors/metabolism ; *Transcription, Genetic
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-08-11
    Description: Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. The combinatorial nature of histone amino-terminal modifications thus reveals a "histone code" that considerably extends the information potential of the genetic code. We propose that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jenuwein, T -- Allis, C D -- GM53512/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1074-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter, Dr. Bohrgasse 7, A-1030 Vienna, Austria. jenuwein@nt.imp.univie.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498575" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Animals ; Chromatin/chemistry/metabolism/ultrastructure ; *Gene Expression Regulation ; *Gene Silencing ; Genomic Imprinting ; Histones/chemistry/genetics/*metabolism ; Methylation ; Molecular Sequence Data ; Phosphorylation ; Protein Structure, Tertiary ; Transcription, Genetic ; Transcriptional Activation
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  • 70
    Publication Date: 2001-11-10
    Description: We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, W -- Chen, H -- Du, K -- Asahara, H -- Tini, M -- Emerson, B M -- Montminy, M -- Evans, R M -- 9R01DK57978/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2507-11. Epub 2001 Nov 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Department of Biological Chemistry, University of California Davis Cancer Center/Basic Science, Sacramento, CA 95817, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11701890" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyltransferases/metabolism ; Amino Acid Sequence ; Animals ; Apoptosis ; Cell Line ; Cyclic AMP Response Element-Binding Protein/metabolism ; Dimerization ; E1A-Associated p300 Protein ; *Gene Expression Regulation ; Genes, Reporter ; Histone Acetyltransferases ; Histones/metabolism ; Methylation ; Molecular Sequence Data ; Nerve Growth Factor/pharmacology ; Nuclear Proteins/chemistry/*metabolism ; PC12 Cells ; Protein Structure, Tertiary ; Protein-Arginine N-Methyltransferases/*metabolism ; Rats ; Receptors, Retinoic Acid/*metabolism ; Recombinant Fusion Proteins/metabolism ; Retinoid X Receptors ; *Saccharomyces cerevisiae Proteins ; Signal Transduction ; Somatostatin/genetics ; Trans-Activators/chemistry/*metabolism ; Transcription Factors/metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Transfection ; Tretinoin/metabolism/pharmacology
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  • 71
    Publication Date: 2001-05-12
    Description: Telomere proteins from ciliated protozoa bind to the single-stranded G-rich DNA extensions at the ends of macronuclear chromosomes. We have now identified homologous proteins in fission yeast and in humans. These Pot1 (protection of telomeres) proteins each bind the G-rich strand of their own telomeric repeat sequence, consistent with a direct role in protecting chromosome ends. Deletion of the fission yeast pot1+ gene has an immediate effect on chromosome stability, causing rapid loss of telomeric DNA and chromosome circularization. It now appears that the protein that caps the ends of chromosomes is widely dispersed throughout the eukaryotic kingdom.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baumann, P -- Cech, T R -- New York, N.Y. -- Science. 2001 May 11;292(5519):1171-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11349150" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chromosome Segregation/genetics ; Chromosomes, Fungal/genetics/metabolism ; Cloning, Molecular ; DNA/genetics/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Electrophoresis, Gel, Pulsed-Field ; Female ; Gene Deletion ; Gene Expression Profiling ; Heterozygote ; Humans ; Molecular Sequence Data ; Ovary/metabolism ; Phenotype ; RNA, Messenger/analysis/genetics ; Schizosaccharomyces/*genetics ; Schizosaccharomyces pombe Proteins ; Sequence Alignment ; Substrate Specificity ; Telomere/genetics/*metabolism ; *Telomere-Binding Proteins
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  • 72
    Publication Date: 2001-06-02
    Description: Transcription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF). A 66-kilodalton subunit of NELF (NELF-A) shows limited sequence similarity to hepatitis delta antigen (HDAg), the viral protein required for replication of hepatitis delta virus (HDV). The host RNAPII has been implicated in HDV replication, but the detailed mechanism and the role of HDAg in this process are not understood. We show that HDAg binds RNAPII directly and stimulates transcription by displacing NELF and promoting RNAPII elongation. These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamaguchi, Y -- Filipovska, J -- Yano, K -- Furuya, A -- Inukai, N -- Narita, T -- Wada, T -- Sugimoto, S -- Konarska, M M -- Handa, H -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):124-7. Epub 2001 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Frontier Collaborative Research Center, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8503, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387440" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Consensus Sequence/genetics ; Enzyme Activation ; HeLa Cells ; Hepatitis Antigens/chemistry/*metabolism ; *Hepatitis Delta Virus/chemistry/genetics/metabolism ; Hepatitis delta Antigens ; Humans ; Molecular Sequence Data ; Protein Binding ; Protein Subunits ; RNA Polymerase II/*metabolism ; RNA, Viral/biosynthesis/genetics ; Sequence Alignment ; Templates, Genetic ; Transcription Factors/antagonists & inhibitors/chemistry/metabolism ; *Transcription, Genetic ; Virus Replication
    Print ISSN: 0036-8075
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  • 73
    Publication Date: 2001-06-26
    Description: Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. This substitution of threonine with isoleucine was sufficient to confer STI-571 resistance in a reconstitution experiment. In three patients, resistance was associated with progressive BCR-ABL gene amplification. These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gorre, M E -- Mohammed, M -- Ellwood, K -- Hsu, N -- Paquette, R -- Rao, P N -- Sawyers, C L -- GM07185/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):876-80. Epub 2001 Jun 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423618" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Antineoplastic Agents/metabolism/pharmacology/therapeutic use ; Base Sequence ; Benzamides ; Blast Crisis/genetics ; Cell Line ; Drug Resistance, Neoplasm/genetics ; Fusion Proteins, bcr-abl/*metabolism ; Gene Amplification ; *Genes, abl ; Humans ; Hydrogen Bonding ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/*genetics ; Molecular Sequence Data ; Philadelphia Chromosome ; Phosphorylation ; Piperazines/metabolism/*pharmacology/therapeutic use ; Point Mutation ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-abl/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Proto-Oncogene Proteins c-crk ; Pyrimidines/metabolism/*pharmacology/therapeutic use ; Recurrence ; Signal Transduction
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  • 74
    Publication Date: 2001-06-09
    Description: The p53 protein is present in low amounts in normally growing cells and is activated in response to physiological insults. MDM2 regulates p53 either through inhibiting p53's transactivating function in the nucleus or by targeting p53 degradation in the cytoplasm. We identified a previously unknown nuclear export signal (NES) in the amino terminus of p53, spanning residues 11 to 27 and containing two serine residues phosphorylated after DNA damage, which was required for p53 nuclear export in colloboration with the carboxyl-terminal NES. Serine-15-phosphorylated p53 induced by ultraviolet irradiation was not exported. Thus, DNA damage-induced phosphorylation may achieve optimal p53 activation by inhibiting both MDM2 binding to, and the nuclear export of, p53.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Y -- Xiong, Y -- CA65572/CA/NCI NIH HHS/ -- K01 CA087580/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1910-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397945" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Animals ; Cell Fusion ; Cell Line ; Cell Nucleus/*metabolism ; Cells, Cultured ; Cytoplasm/metabolism ; *DNA Damage ; Mice ; Molecular Sequence Data ; Mutation ; *Nuclear Proteins ; Phosphorylation ; Phosphoserine/metabolism ; *Protein Sorting Signals ; Protein Structure, Tertiary ; Proteins/genetics/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Recombinant Fusion Proteins/metabolism ; Transfection ; Tumor Suppressor Protein p14ARF ; Tumor Suppressor Protein p53/*chemistry/genetics/*metabolism ; Ubiquitins/metabolism ; Ultraviolet Rays
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  • 75
    Publication Date: 2001-03-27
    Description: During its development, a plant shoot progresses from a juvenile to an adult phase of vegetative growth and from a reproductively incompetent to a reproductively competent state. In Arabidopsis, loss-of-function mutations in SQUINT (SQN) reduced the number of juvenile leaves and had subtle effects on inflorescence morphology but had no effect on flowering time or on reproductive competence. SQN encodes the Arabidopsis homolog of cyclophilin 40 (CyP40), a protein found in association with the Hsp90 chaperone complex in yeast, mammals, and plants. Thus, in Arabidopsis, CyP40 is specifically required for the vegetative but not the reproductive maturation of the shoot.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berardini, T Z -- Bollman, K -- Sun, H -- Poethig, R S -- R01-GM1893-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 23;291(5512):2405-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Science Institute, Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA. spoethig@sas.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11264535" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/anatomy & histology/*genetics/*growth & development/physiology ; Carrier Proteins/chemistry/genetics/physiology ; Chromosome Mapping ; *Cyclophilins ; Exons ; Gene Expression Regulation, Plant ; Genes, Plant ; Heat-Shock Proteins/genetics ; Molecular Sequence Data ; Mutation ; Peptidylprolyl Isomerase/chemistry/genetics/physiology ; Phenotype ; Plant Leaves/anatomy & histology/growth & development ; Plant Shoots/growth & development/physiology ; Reproduction ; Sequence Alignment ; Temperature
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  • 76
    Publication Date: 2001-12-01
    Description: Heterotrimeric GTP-binding proteins (G proteins) control cellular functions by transducing signals from the outside to the inside of cells. Regulator of G protein signaling (RGS) proteins are key modulators of the amplitude and duration of G protein-mediated signaling through their ability to serve as guanosine triphosphatase-activating proteins (GAPs). We have identified RGS-PX1, a Galpha(s)-specific GAP. The RGS domain of RGS-PX1 specifically interacted with Galpha(s), accelerated its GTP hydrolysis, and attenuated Galpha(s)-mediated signaling. RGS-PX1 also contains a Phox (PX) domain that resembles those in sorting nexin (SNX) proteins. Expression of RGS-PX1 delayed lysosomal degradation of the EGF receptor. Because of its bifunctional role as both a GAP and a SNX, RGS-PX1 may link heterotrimeric G protein signaling and vesicular trafficking.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, B -- Ma, Y C -- Ostrom, R S -- Lavoie, C -- Gill, G N -- Insel, P A -- Huang, X Y -- Farquhar, M G -- AG14563/AG/NIA NIH HHS/ -- CA58689/CA/NCI NIH HHS/ -- DK17780/DK/NIDDK NIH HHS/ -- GM56904/GM/NIGMS NIH HHS/ -- HL53773/HL/NHLBI NIH HHS/ -- HL63885/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 30;294(5548):1939-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11729322" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor Agonists ; Amino Acid Sequence ; Animals ; COS Cells ; Carrier Proteins/chemistry/*metabolism ; Cattle ; Cell Line ; Cyclic AMP/metabolism ; Endosomes/chemistry/metabolism ; GTP-Binding Protein alpha Subunits, Gs/antagonists & inhibitors/*metabolism ; GTPase-Activating Proteins/chemistry/*metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Sequence Data ; Protein Binding ; Protein Interaction Mapping ; Protein Structure, Tertiary ; Protein Transport ; RGS Proteins/chemistry/*metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Receptors, Adrenergic, beta-2/genetics/metabolism ; Sequence Alignment ; Signal Transduction ; Sorting Nexins ; Substrate Specificity ; *Vesicular Transport Proteins
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  • 77
    Publication Date: 2001-08-04
    Description: The development of resistance is the main threat to the long-term use of toxins from Bacillus thuringiensis (Bt) in transgenic plants. Here we report the cloning of a Bt toxin resistance gene, Caenorhabditis elegans bre-5, which encodes a putative beta-1,3-galactosyltransferase. Lack of bre-5 in the intestine led to resistance to the Bt toxin Cry5B. Wild-type but not bre-5 mutant animals were found to uptake toxin into their gut cells, consistent with bre-5 mutants lacking toxin-binding sites on their apical gut. bre-5 mutants displayed resistance to Cry14A, a Bt toxin lethal to both nematodes and insects; this indicates that resistance by loss of carbohydrate modification is relevant to multiple Bt toxins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffitts, J S -- Whitacre, J L -- Stevens, D E -- Aroian, R V -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):860-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11486087" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacterial Proteins/metabolism/*toxicity ; *Bacterial Toxins ; Biological Transport ; Caenorhabditis elegans/enzymology/*genetics/metabolism ; *Caenorhabditis elegans Proteins ; Cloning, Molecular ; Digestive System/enzymology/metabolism ; Disorders of Sex Development ; Drug Resistance/genetics ; Endocytosis ; Endotoxins/metabolism/*toxicity ; Feeding Behavior ; Galactosyltransferases/chemistry/*genetics/*metabolism ; Genes, Helminth ; Hemolysin Proteins ; *Insect Proteins ; Molecular Sequence Data ; Mosaicism ; Mutation ; *Pest Control, Biological ; Receptors, Cell Surface/metabolism ; Transformation, Genetic
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  • 78
    Publication Date: 2001-06-02
    Description: The GGAs are a multidomain protein family implicated in protein trafficking between the Golgi and endosomes. Here, the VHS domain of GGA2 was shown to bind to the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CI-MPR). Receptors with mutations in this motif were defective in lysosomal enzyme sorting. The hinge domain of GGA2 bound clathrin, suggesting that GGA2 could be a link between cargo molecules and clathrin-coated vesicle assembly. Thus, GGA2 binding to the CI-MPR is important for lysosomal enzyme targeting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Y -- Doray, B -- Poussu, A -- Lehto, V P -- Kornfeld, S -- R01 CA-08759/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 1;292(5522):1716-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387476" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; *Carrier Proteins ; Cations ; Clathrin/metabolism ; Dipeptides/chemistry/metabolism ; L Cells (Cell Line) ; Lysosomes/*enzymology ; Mice ; Molecular Sequence Data ; Mutation ; Protein Sorting Signals ; Protein Structure, Tertiary ; *Protein Transport ; Proteins/chemistry/genetics/*metabolism ; Rats ; Receptor, IGF Type 2/*chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Solubility ; Transcription Factor AP-1/metabolism ; Transport Vesicles/metabolism ; Two-Hybrid System Techniques ; trans-Golgi Network/metabolism
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  • 79
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-06-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thornton, J M -- New York, N.Y. -- Science. 2001 Jun 15;292(5524):2095-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College Department of Biochemistry and Molecular Biology, London WC1E 6BT, UK. thornton@biochem.ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11408660" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Computational Biology ; Computer Simulation ; Databases, Factual ; Evolution, Molecular ; Genome ; *Models, Molecular ; Peptide Library ; *Protein Conformation ; Protein Structure, Tertiary ; Proteins/*chemistry/*physiology ; Proteome ; Sequence Homology, Amino Acid
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  • 80
    Publication Date: 2001-08-18
    Description: B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, J S -- Bixler, S A -- Qian, F -- Vora, K -- Scott, M L -- Cachero, T G -- Hession, C -- Schneider, P -- Sizing, I D -- Mullen, C -- Strauch, K -- Zafari, M -- Benjamin, C D -- Tschopp, J -- Browning, J L -- Ambrose, C -- New York, N.Y. -- Science. 2001 Sep 14;293(5537):2108-11. Epub 2001 Aug 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biogen, 12 Cambridge Center, Cambridge, MA 02142, USA., The Institute of Biochemistry, University of Lausanne, CH-1066, Epalinges, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11509692" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Cell Activating Factor ; B-Cell Activation Factor Receptor ; B-Cell Maturation Antigen ; B-Lymphocytes/immunology/metabolism/*physiology ; Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 22 ; Cloning, Molecular ; Homeostasis ; Humans ; Ligands ; Lymphoid Tissue/metabolism ; Male ; Membrane Proteins/*metabolism ; Mice ; Mice, Inbred A ; Mice, Inbred C57BL ; Molecular Sequence Data ; RNA, Messenger/chemistry/genetics/metabolism ; Receptors, Tumor Necrosis Factor/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Transfection ; Transmembrane Activator and CAML Interactor Protein ; Tumor Necrosis Factor-alpha/*metabolism
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  • 81
    Publication Date: 2001-09-05
    Description: The developmental signaling functions of cell surface heparan sulfate proteoglycans (HSPGs) are dependent on their sulfation states. Here, we report the identification of QSulf1, the avian ortholog of an evolutionarily conserved protein family related to heparan-specific N-acetyl glucosamine sulfatases. QSulf1 expression is induced by Sonic hedgehog in myogenic somite progenitors in quail embryos and is required for the activation of MyoD, a Wnt-induced regulator of muscle specification. QSulf1 is localized on the cell surface and regulates heparan-dependent Wnt signaling in C2C12 myogenic progenitor cells through a mechanism that requires its catalytic activity, providing evidence that QSulf1 regulates Wnt signaling through desulfation of cell surface HSPGs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dhoot, G K -- Gustafsson, M K -- Ai, X -- Sun, W -- Standiford, D M -- Emerson , C P Jr -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1663-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Basic Veterinary Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 OTU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533491" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Body Patterning ; CHO Cells ; Cell Membrane/metabolism ; Cells, Cultured ; Cloning, Molecular ; Coculture Techniques ; Cricetinae ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Hedgehog Proteins ; Heparan Sulfate Proteoglycans/*metabolism ; Heparin/metabolism/pharmacology ; Heparitin Sulfate/metabolism ; Molecular Sequence Data ; Muscles/cytology/*embryology/metabolism ; Mutation ; MyoD Protein/genetics/metabolism ; Oligonucleotides, Antisense ; Proto-Oncogene Proteins/*metabolism ; Quail/*embryology ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; *Signal Transduction ; Somites/metabolism ; Stem Cells/*metabolism ; Sulfatases/chemistry/genetics/*metabolism ; Trans-Activators/genetics/metabolism ; Transfection ; Wnt Proteins ; *Zebrafish Proteins
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  • 82
    Publication Date: 2001-06-30
    Description: The pollen extracellular matrix contains proteins mediating species specificity and components needed for efficient pollination. We identified all proteins 〉10 kilodaltons in the Arabidopsis pollen coating and showed that most of the corresponding genes reside in two genomic clusters. One cluster encodes six lipases, whereas the other contains six lipid-binding oleosin genes, including GRP17, a gene that promotes efficient pollination. Individual oleosins exhibit extensive divergence between ecotypes, but the entire cluster remains intact. Analysis of the syntenic region in Brassica oleracea revealed even greater divergence, but a similar clustering of the genes. Such allelic flexibility may promote speciation in plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayfield, J A -- Fiebig, A -- Johnstone, S E -- Preuss, D -- New York, N.Y. -- Science. 2001 Jun 29;292(5526):2482-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11431566" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/chemistry/*genetics ; *Arabidopsis Proteins ; Brassica/chemistry/genetics ; Expressed Sequence Tags ; Genes, Plant ; Genetic Variation ; Genome, Plant ; Lipase/*chemistry/genetics ; Molecular Sequence Data ; *Multigene Family ; Phosphotransferases/chemistry/genetics ; Plant Proteins/*chemistry/genetics ; Pollen/*chemistry ; Protein Structure, Tertiary ; *Proteome ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment
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  • 83
    Publication Date: 2001-02-07
    Description: The disulfide reducing enzymes glutathione reductase and thioredoxin reductase are highly conserved among bacteria, fungi, worms, and mammals. These proteins maintain intracellular redox homeostasis to protect the organism from oxidative damage. Here we demonstrate the absence of glutathione reductase in Drosophila melanogaster, identify a new type of thioredoxin reductase, and provide evidence that a thioredoxin system supports GSSG reduction. Our data suggest that antioxidant defense in Drosophila, and probably in related insects, differs fundamentally from that in other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kanzok, S M -- Fechner, A -- Bauer, H -- Ulschmid, J K -- Muller, H M -- Botella-Munoz, J -- Schneuwly, S -- Schirmer, R -- Becker, K -- New York, N.Y. -- Science. 2001 Jan 26;291(5504):643-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center of Biochemistry, Im Neuenheimer Feld 328, Heidelberg University, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11158675" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Binding Sites ; Drosophila melanogaster/*enzymology/genetics/metabolism ; Genes, Insect ; Glutathione/*metabolism ; Glutathione Disulfide/metabolism ; Glutathione Reductase/*metabolism ; Humans ; Kinetics ; Molecular Sequence Data ; Mutation ; NADP/metabolism ; Oxidation-Reduction ; Sequence Alignment ; Species Specificity ; Substrate Specificity ; Thioredoxin-Disulfide Reductase/antagonists & ; inhibitors/chemistry/*genetics/*metabolism
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  • 84
    Publication Date: 2001-09-08
    Description: Bcl-2 family members bearing only the BH3 domain are essential inducers of apoptosis. We identified a BH3-only protein, Bmf, and show that its BH3 domain is required both for binding to prosurvival Bcl-2 proteins and for triggering apoptosis. In healthy cells, Bmf is sequestered to myosin V motors by association with dynein light chain 2. Certain damage signals, such as loss of cell attachment (anoikis), unleash Bmf, allowing it to translocate and bind prosurvival Bcl-2 proteins. Thus, at least two mammalian BH3-only proteins, Bmf and Bim, function to sense intracellular damage by their localization to distinct cytoskeletal structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puthalakath, H -- Villunger, A -- O'Reilly, L A -- Beaumont, J G -- Coultas, L -- Cheney, R E -- Huang, D C -- Strasser, A -- CA 80188/CA/NCI NIH HHS/ -- R29 DC003299/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 7;293(5536):1829-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter and Eliza Hall Institute of Medical Research, Melbourne, P.O. Royal Melbourne Hospital, 3050 VIC, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11546872" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; *Anoikis ; Apoptosis Regulatory Proteins ; Calmodulin-Binding Proteins/*metabolism ; Carrier Proteins/*chemistry/genetics/*metabolism ; Cell Line ; Cytoskeleton/metabolism ; *Drosophila Proteins ; Dyneins ; Gene Expression Profiling ; Humans ; *Membrane Proteins ; Mice ; Molecular Motor Proteins/*metabolism ; Molecular Sequence Data ; Mutation ; Myeloid Cell Leukemia Sequence 1 Protein ; *Myosin Type V ; Neoplasm Proteins/genetics/metabolism ; Nerve Tissue Proteins/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Protein Transport ; *Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-2/chemistry/genetics/metabolism ; RNA, Messenger/analysis/genetics ; Transfection ; Two-Hybrid System Techniques
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  • 85
    Publication Date: 2001-05-12
    Description: Epigenetic silenced alleles of the Arabidopsis SUPERMAN locus (the clark kent alleles) are associated with dense hypermethylation at noncanonical cytosines (CpXpG and asymmetric sites, where X = A, T, C, or G). A genetic screen for suppressors of a hypermethylated clark kent mutant identified nine loss-of-function alleles of CHROMOMETHYLASE3 (CMT3), a novel cytosine methyltransferase homolog. These cmt3 mutants display a wild-type morphology but exhibit decreased CpXpG methylation of the SUP gene and of other sequences throughout the genome. They also show reactivated expression of endogenous retrotransposon sequences. These results show that a non-CpG DNA methyltransferase is responsible for maintaining epigenetic gene silencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindroth, A M -- Cao, X -- Jackson, J P -- Zilberman, D -- McCallum, C M -- Henikoff, S -- Jacobsen, S E -- GM07104/GM/NIGMS NIH HHS/ -- GM07185/GM/NIGMS NIH HHS/ -- GM29009/GM/NIGMS NIH HHS/ -- GM60398/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 15;292(5524):2077-80. Epub 2001 May 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11349138" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Arabidopsis/*genetics/metabolism ; *Arabidopsis Proteins ; Base Sequence ; Chromosome Mapping ; Cloning, Molecular ; CpG Islands ; Crosses, Genetic ; Cytosine/metabolism ; *DNA Methylation ; DNA-Cytosine Methylases/chemistry/*genetics/*metabolism ; Dinucleoside Phosphates/metabolism ; Gene Expression Regulation, Plant ; *Gene Silencing ; Genes, Plant ; Molecular Sequence Data ; Mutagenesis ; Oligonucleotides/*metabolism ; Phenotype ; Protein Structure, Tertiary ; Retroelements ; Transcription Factors/*genetics
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  • 86
    Publication Date: 2001-10-27
    Description: ErbB-4 is a transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation. After binding of its ligand heregulin (HRG) or activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA), the ErbB-4 ectodomain is cleaved by a metalloprotease. We now report a subsequent cleavage by gamma-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. gamma-Secretase cleavage was prevented by chemical inhibitors or a dominant negative presenilin. Inhibition of gamma-secretase also prevented growth inhibition by HRG. gamma-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase-mediated signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ni, C Y -- Murphy, M P -- Golde, T E -- Carpenter, G -- CA24071/CA/NCI NIH HHS/ -- CA68485/CA/NCI NIH HHS/ -- DK20593/DK/NIDDK NIH HHS/ -- NS39072/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 7;294(5549):2179-81. Epub 2001 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11679632" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Amyloid Precursor Protein Secretases ; Animals ; Aspartic Acid Endopeptidases ; COS Cells ; Carbamates/pharmacology ; Cell Division/drug effects ; Cell Line ; Cell Membrane/metabolism ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; Dipeptides/pharmacology ; Endopeptidases/*metabolism ; Fatty Acids, Unsaturated/pharmacology ; Humans ; Membrane Proteins/genetics/metabolism ; Metalloendopeptidases/metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Neuregulin-1/pharmacology ; Presenilin-1 ; Protease Inhibitors/pharmacology ; Protein Structure, Tertiary ; Receptor, Epidermal Growth Factor/chemistry/*metabolism ; Receptor, ErbB-4 ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Tetradecanoylphorbol Acetate/pharmacology ; Transcriptional Activation ; Tumor Cells, Cultured
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  • 87
    Publication Date: 2001-02-27
    Description: Bag (Bcl2-associated athanogene) domains occur in a class of cofactors of the eukaryotic chaperone 70-kilodalton heat shock protein (Hsp70) family. Binding of the Bag domain to the Hsp70 adenosine triphosphatase (ATPase) domain promotes adenosine 5'-triphosphate-dependent release of substrate from Hsp70 in vitro. In a 1.9 angstrom crystal structure of a complex with the ATPase of the 70-kilodalton heat shock cognate protein (Hsc70), the Bag domain forms a three-helix bundle, inducing a conformational switch in the ATPase that is incompatible with nucleotide binding. The same switch is observed in the bacterial Hsp70 homolog DnaK upon binding of the structurally unrelated nucleotide exchange factor GrpE. Thus, functional convergence has allowed proteins with different architectures to trigger a conserved conformational shift in Hsp70 that leads to nucleotide exchange.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sondermann, H -- Scheufler, C -- Schneider, C -- Hohfeld, J -- Hartl, F U -- Moarefi, I -- New York, N.Y. -- Science. 2001 Feb 23;291(5508):1553-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max-Planck-Institut fur Biochemie, D-82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11222862" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphatases/*chemistry/*metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Bacterial Proteins/chemistry/metabolism ; Carrier Proteins/*chemistry/*metabolism ; Cattle ; Crystallography, X-Ray ; DNA-Binding Proteins ; *Escherichia coli Proteins ; Evolution, Molecular ; HSC70 Heat-Shock Proteins ; HSP70 Heat-Shock Proteins/*chemistry/*metabolism ; Heat-Shock Proteins/chemistry/metabolism ; Humans ; Hydrolysis ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Isoforms ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Transcription Factors
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  • 88
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Catterall, W A -- New York, N.Y. -- Science. 2001 Dec 14;294(5550):2306-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, WA 98195, USA. wcatt@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11743190" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Bacillus/*chemistry/metabolism ; Bacterial Proteins/antagonists & inhibitors/chemistry/*metabolism ; Calcium Channels/chemistry/metabolism ; Ion Channel Gating ; Ion Transport ; Membrane Potentials ; Potassium Channel Blockers ; Potassium Channels/chemistry/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sodium/*metabolism ; Sodium Channel Blockers ; Sodium Channels/*chemistry/*metabolism ; Static Electricity
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  • 89
    Publication Date: 2001-09-05
    Description: Cardiac valve formation is a complex process that involves cell signaling events between the myocardial and endocardial layers of the heart across an elaborate extracellular matrix. These signals lead to marked morphogenetic movements and transdifferentiation of the endocardial cells at chamber boundaries. Here we identify the genetic defect in zebrafish jekyll mutants, which are deficient in the initiation of heart valve formation. The jekyll mutation disrupts a homolog of Drosophila Sugarless, a uridine 5'-diphosphate (UDP)-glucose dehydrogenase required for heparan sulfate, chondroitin sulfate, and hyaluronic acid production. The atrioventricular border cells do not differentiate from their neighbors in jekyll mutants, suggesting that Jekyll is required in a cell signaling event that establishes a boundary between the atrium and ventricle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walsh, E C -- Stainier, D Y -- HL54737/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1670-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, CA 94143-0448, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533493" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antisense Elements (Genetics) ; Body Patterning ; Bone Morphogenetic Proteins/genetics ; Endocardium/embryology/metabolism ; Female ; Gene Expression ; Glycosaminoglycans/metabolism ; Heart/*embryology ; Heart Valves/cytology/*embryology/enzymology/metabolism ; Male ; Molecular Sequence Data ; Morphogenesis ; Mutation ; Myocardium/cytology/metabolism ; Phenotype ; Physical Chromosome Mapping ; Signal Transduction ; Uridine Diphosphate Glucose Dehydrogenase/*genetics/*metabolism ; Zebrafish/*embryology/genetics
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  • 90
    Publication Date: 2001-08-04
    Description: One of the most dominant influences in the patterning of multicellular embryos is exerted by the Hedgehog (Hh) family of secreted signaling proteins. Here, we identify a segment polarity gene in Drosophila melanogaster, skinny hedgehog (ski), and show that its product is required in Hh-expressing cells for production of appropriate signaling activity in embryos and in the imaginal precursors of adult tissues. The ski gene encodes an apparent acyltransferase, and we provide genetic and biochemical evidence that Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification. Our results suggest that ski encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of Hh, and further demonstrate that this lipid modification is required for the embryonic and larval patterning activities of the Hh signal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chamoun, Z -- Mann, R K -- Nellen, D -- von Kessler, D P -- Bellotto, M -- Beachy, P A -- Basler, K -- New York, N.Y. -- Science. 2001 Sep 14;293(5537):2080-4. Epub 2001 Aug 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Molekularbiologie and Zoologisches Institut, Universitat Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11486055" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Acyltransferases/chemistry/*genetics/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Body Patterning ; Cholesterol/metabolism ; *Drosophila Proteins ; Drosophila melanogaster/embryology/*genetics/growth & development/metabolism ; Gene Expression ; Genes, Insect ; Hedgehog Proteins ; Insect Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Palmitic Acid/*metabolism ; Protein Structure, Tertiary ; *Signal Transduction ; Transgenes
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  • 91
    Publication Date: 2001-06-02
    Description: Acetylation of core histone tails plays a fundamental role in transcription regulation. In addition to acetylation, other posttranslational modifications, such as phosphorylation and methylation, occur in core histone tails. Here, we report the purification, molecular identification, and functional characterization of a histone H4-specific methyltransferase PRMT1, a protein arginine methyltransferase. PRMT1 specifically methylates arginine 3 (Arg 3) of H4 in vitro and in vivo. Methylation of Arg 3 by PRMT1 facilitates subsequent acetylation of H4 tails by p300. However, acetylation of H4 inhibits its methylation by PRMT1. Most important, a mutation in the S-adenosyl-l-methionine-binding site of PRMT1 substantially crippled its nuclear receptor coactivator activity. Our finding reveals Arg 3 of H4 as a novel methylation site by PRMT1 and indicates that Arg 3 methylation plays an important role in transcriptional regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, H -- Huang, Z Q -- Xia, L -- Feng, Q -- Erdjument-Bromage, H -- Strahl, B D -- Briggs, S D -- Allis, C D -- Wong, J -- Tempst, P -- Zhang, Y -- GM63067-01/GM/NIGMS NIH HHS/ -- P30 CA08748/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 3;293(5531):853-7. Epub 2001 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387442" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Animals ; Arginine/*metabolism ; Binding Sites ; Cell Nucleus/metabolism ; HeLa Cells ; Histones/chemistry/*metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Intracellular Signaling Peptides and Proteins ; Lysine/metabolism ; Methylation ; Methyltransferases/chemistry/genetics/isolation & purification/*metabolism ; Molecular Sequence Data ; Mutation ; Oocytes ; Protein-Arginine N-Methyltransferases ; Receptors, Androgen/*metabolism ; Recombinant Proteins/metabolism ; S-Adenosylmethionine/metabolism ; *Transcriptional Activation ; Xenopus
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  • 92
    Publication Date: 2001-09-08
    Description: Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. To better elucidate the structural basis for the "flip-flop" mechanism of substrate movement across the lipid bilayer, we have determined the structure of the lipid flippase MsbA from Escherichia coli by x-ray crystallography to a resolution of 4.5 angstroms. MsbA is organized as a homodimer with each subunit containing six transmembrane alpha-helices and a nucleotide-binding domain. The asymmetric distribution of charged residues lining a central chamber suggests a general mechanism for the translocation of substrate by MsbA and other MDR-ABC transporters. The structure of MsbA can serve as a model for the MDR-ABC transporters that confer multidrug resistance to cancer cells and infectious microorganisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, G -- Roth, C B -- GM61905-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Sep 7;293(5536):1793-800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, MB-9, The Scripps Research Institute, La Jolla, CA 92037, USA. gchang@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11546864" target="_blank"〉PubMed〈/a〉
    Keywords: *ATP-Binding Cassette Transporters ; Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/metabolism ; Binding Sites ; Biological Transport ; Crystallography, X-Ray ; Dimerization ; *Drug Resistance, Microbial ; *Drug Resistance, Multiple ; Escherichia coli/*enzymology ; Lipid A/metabolism ; Membrane Proteins/*chemistry/genetics/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sequence Alignment ; Static Electricity ; Structure-Activity Relationship
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  • 93
    Publication Date: 2001-06-26
    Description: Recent studies in bacterial pathogenesis reveal common and contrasting mechanisms of pathogen virulence and host resistance in plant and animal diseases. This review presents recent developments in the study of plant and animal pathogenesis, with respect to bacterial colonization and the delivery of effector proteins to the host. Furthermore, host defense responses in both plants and animals are discussed in relation to mechanisms of pathogen recognition and defense signaling. Future studies will greatly add to our understanding of the molecular events defining host-pathogen interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Staskawicz, B J -- Mudgett, M B -- Dangl, J L -- Galan, J E -- New York, N.Y. -- Science. 2001 Jun 22;292(5525):2285-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, University of California at Berkeley, Berkeley, CA 94720, USA. stask@nature.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11423652" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacteria/genetics/metabolism/*pathogenicity ; Bacterial Infections/immunology/microbiology ; Bacterial Proteins/chemistry/genetics/metabolism ; Genes, Bacterial ; Genes, Plant ; Immunity, Innate ; Molecular Sequence Data ; Plant Diseases/*microbiology ; Plant Proteins/chemistry/genetics/metabolism ; Plants/genetics/metabolism/*microbiology ; Proteins/genetics/metabolism ; Virulence
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  • 94
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-06-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finlay, B B -- New York, N.Y. -- Science. 2001 Jun 1;292(5522):1665-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotechnology Laboratory, University of British Columbia, Vancouver, V6T 1Z3, British Columbia, Canada. bfinlay@interchange.ubc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11387462" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Bacterial Proteins/chemistry/*metabolism ; Bacterial Translocation ; Cadherins/chemistry/genetics/*metabolism ; Carrier Proteins/genetics ; Cell Line ; *Disease Models, Animal ; Fatty Acid-Binding Proteins ; Guinea Pigs ; Humans ; Intestinal Mucosa/cytology/metabolism/*microbiology ; Intestine, Small/cytology/metabolism/microbiology ; Listeria monocytogenes/metabolism/*pathogenicity ; Listeriosis/*microbiology ; Mice ; Mice, Transgenic ; *Neoplasm Proteins ; *Nerve Tissue Proteins ; Promoter Regions, Genetic ; *Tumor Suppressor Proteins ; Virulence
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  • 95
    Publication Date: 2001-09-05
    Description: Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G1 phase to the S phase of the cell cycle. The amount of cyclin E protein present in the cell is tightly controlled by ubiquitin-mediated proteolysis. Here we identify the ubiquitin ligase responsible for cyclin E ubiquitination as SCFFbw7 and demonstrate that it is functionally conserved in yeast, flies, and mammals. Fbw7 associates specifically with phosphorylated cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro. Depletion of Fbw7 leads to accumulation and stabilization of cyclin E in vivo in human and Drosophila melanogaster cells. Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koepp, D M -- Schaefer, L K -- Ye, X -- Keyomarsi, K -- Chu, C -- Harper, J W -- Elledge, S J -- R01 AG011085/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2001 Oct 5;294(5540):173-7. Epub 2001 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533444" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Breast Neoplasms/genetics/metabolism ; *CDC2-CDC28 Kinases ; *Cell Cycle ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Cell Line ; Cyclin E/*metabolism ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinases/metabolism ; Drosophila Proteins ; Drosophila melanogaster ; *F-Box Proteins ; Humans ; Mice ; Molecular Sequence Data ; Peptide Synthases/chemistry/genetics/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/metabolism ; RNA, Double-Stranded ; Recombinant Fusion Proteins/metabolism ; SKP Cullin F-Box Protein Ligases ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins ; Sequence Alignment ; Transfection ; Tumor Cells, Cultured ; *Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism
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  • 96
    Publication Date: 2001-07-07
    Description: In the visual system, the establishment of the anteroposterior and dorsoventral axes in the retina and tectum during development is important for topographic retinotectal projection. We identified chick Ventroptin, an antagonist of bone morphogenetic protein 4 (BMP-4), which is mainly expressed in the ventral retina, not only with a ventral high-dorsal low gradient but also with a nasal high-temporal low gradient at later stages. Misexpression of Ventroptin altered expression patterns of several topographic genes in the retina and projection of the retinal axons to the tectum along both axes. Thus, the topographic retinotectal projection appears to be specified by the double-gradient molecule Ventroptin along the two axes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakuta, H -- Suzuki, R -- Takahashi, H -- Kato, A -- Shintani, T -- Iemura Si -- Yamamoto, T S -- Ueno, N -- Noda, M -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):111-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Neurobiology, National Institute for Basic Biology, The Graduate University for Advanced Studies, 38 Nishigonaka, Myodaiji-cho, Okazaki 444-8585, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441185" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; Animals ; Bone Morphogenetic Protein 4 ; Bone Morphogenetic Proteins/*antagonists & inhibitors/genetics/metabolism ; Chick Embryo ; Cloning, Molecular ; Electroporation ; Embryo, Nonmammalian/cytology/metabolism ; Eye Proteins/chemistry/genetics/*metabolism ; *Gene Expression Regulation, Developmental ; Gene Library ; Humans ; In Situ Hybridization ; Mice ; Microinjections ; Molecular Sequence Data ; *Morphogenesis ; Nerve Tissue Proteins ; Precipitin Tests ; Protein Binding ; Protein Isoforms/chemistry/genetics/metabolism ; RNA, Messenger/analysis/genetics ; Retina/*embryology/*metabolism ; Sequence Alignment ; Surface Plasmon Resonance ; Xenopus Proteins ; Xenopus laevis/embryology/metabolism
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  • 97
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2001-03-07
    Description: Human immunodeficiency virus type-1 (HIV-1) membrane fusion is promoted by the formation of a trimer-of-hairpins structure that brings the amino- and carboxyl-terminal regions of the gp41 envelope glycoprotein ectodomain into close proximity. Peptides derived from the carboxyl-terminal region (called C-peptides) potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To test the converse of this inhibitory strategy, we designed a small protein, denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants and may serve as the basis for a new class of antiviral agents. The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Root, M J -- Kay, M S -- Kim, P S -- P01 GM56552/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Feb 2;291(5505):884-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. kimadmin@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11229405" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Anti-HIV Agents/chemistry/immunology/metabolism/pharmacology ; Carrier Proteins/*chemistry/metabolism/*pharmacology ; Cell Line ; *Drug Design ; Giant Cells/drug effects ; HIV Antibodies/immunology ; HIV Envelope Protein gp41/chemistry/*metabolism ; HIV-1/*drug effects/physiology ; Humans ; Membrane Fusion/*drug effects ; Molecular Sequence Data ; Neutralization Tests ; Peptide Fragments/chemistry/immunology/metabolism ; *Peptides ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Tumor Cells, Cultured
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  • 98
    Publication Date: 2002-02-02
    Description: In bacteria, promoter recognition depends on the RNA polymerase sigma subunit, which combines with the catalytically proficient RNA polymerase core to form the holoenzyme. The major class of bacterial promoters is defined by two conserved elements (the -10 and -35 elements, which are 10 and 35 nucleotides upstream of the initiation point, respectively) that are contacted by sigma in the holoenzyme. We show that recognition of promoters of this class depends on the "flexible flap" domain of the RNA polymerase beta subunit. The flap interacts with conserved region 4 of sigma and triggers a conformational change that moves region 4 into the correct position for interaction with the -35 element. Because the flexible flap is evolutionarily conserved, this domain may facilitate promoter recognition by specificity factors in eukaryotes as well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuznedelov, Konstantin -- Minakhin, Leonid -- Niedziela-Majka, Anita -- Dove, Simon L -- Rogulja, Dragana -- Nickels, Bryce E -- Hochschild, Ann -- Heyduk, Tomasz -- Severinov, Konstantin -- GM44025/GM/NIGMS NIH HHS/ -- GM50514/GM/NIGMS NIH HHS/ -- R01 GM044025/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 1;295(5556):855-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823642" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Amino Acid Sequence ; Bacterial Proteins/chemistry/genetics/*metabolism ; DNA, Bacterial/genetics/metabolism ; DNA-Directed RNA Polymerases/chemistry/genetics/*metabolism ; Energy Transfer ; Escherichia coli/*enzymology/genetics ; Holoenzymes/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; *Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Sigma Factor/chemistry/genetics/*metabolism ; *Transcription, Genetic ; Two-Hybrid System Techniques
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  • 99
    Publication Date: 2001-02-13
    Description: We cloned and characterized a protein kinase and ion channel, TRP-PLIK. As part of the long transient receptor potential channel subfamily implicated in control of cell division, it is a protein that is both an ion channel and a protein kinase. TRP-PLIK phosphorylated itself, displayed a wide tissue distribution, and, when expressed in CHO-K1 cells, constituted a nonselective, calcium-permeant, 105-picosiemen, steeply outwardly rectifying conductance. The zinc finger containing alpha-kinase domain was functional. Inactivation of the kinase activity by site-directed mutagenesis and the channel's dependence on intracellular adenosine triphosphate (ATP) demonstrated that the channel's kinase activity is essential for channel function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Runnels, L W -- Yue, L -- Clapham, D E -- New York, N.Y. -- Science. 2001 Feb 9;291(5506):1043-7. Epub 2001 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Cardiology, Department of Neurobiology, Harvard Medical School, 1309 Enders Building, 320 Longwood Avenue, Children's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11161216" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; CHO Cells ; Calcium/metabolism ; Catalytic Domain ; Cations/metabolism ; Cell Line ; Cricetinae ; DNA, Complementary ; Electric Conductivity ; Humans ; Ion Channels/chemistry/*genetics/*metabolism ; *Membrane Proteins ; Mice ; Molecular Sequence Data ; Mutation ; Myelin Basic Protein/metabolism ; Patch-Clamp Techniques ; Phosphorylation ; Protein Kinases/chemistry/*genetics/*metabolism ; Protein-Serine-Threonine Kinases ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; TRPM Cation Channels ; Transfection ; Two-Hybrid System Techniques ; Type C Phospholipases/metabolism
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  • 100
    Publication Date: 2002-09-14
    Description: Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Haijuan -- Jeffrey, Philip D -- Miller, Julie -- Kinnucan, Elspeth -- Sun, Yutong -- Thoma, Nicolas H -- Zheng, Ning -- Chen, Phang-Lang -- Lee, Wen-Hwa -- Pavletich, Nikola P -- New York, N.Y. -- Science. 2002 Sep 13;297(5588):1837-48.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228710" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; BRCA2 Protein/*chemistry/genetics/*metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA/metabolism ; *DNA Repair ; DNA, Single-Stranded/*metabolism ; DNA-Binding Proteins/metabolism ; Genes, BRCA2 ; Helix-Turn-Helix Motifs ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Mice ; Molecular Sequence Data ; Mutation ; Proteasome Endopeptidase Complex ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteins/chemistry/*metabolism ; Rad51 Recombinase ; Rats ; *Recombination, Genetic
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