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  • Protein Conformation  (270)
  • Base Sequence
  • American Association for the Advancement of Science (AAAS)  (409)
  • American Association of Petroleum Geologists (AAPG)
  • 2005-2009  (409)
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  • American Association for the Advancement of Science (AAAS)  (409)
  • American Association of Petroleum Geologists (AAPG)
  • Nature Publishing Group (NPG)  (83)
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  • 1
    Publication Date: 2009-03-17
    Description: The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein-binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species, using hydroxyl radical cleavage patterns to interrogate the solvent-accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained-double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than did regions identified solely on the basis of nucleotide sequence. These results support the idea that the molecular shape of DNA is under selection and can identify evolutionary history.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749491/" 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/PMC2749491/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, Stephen C J -- Hansen, Loren -- Abaan, Hatice Ozel -- Tullius, Thomas D -- Margulies, Elliott H -- R01 HG003541/HG/NHGRI NIH HHS/ -- R01 HG003541-03/HG/NHGRI NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):389-92. doi: 10.1126/science.1169050. Epub 2009 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics Program, Boston University, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286520" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Motifs ; Base Sequence ; Binding Sites ; Conserved Sequence ; DNA/*chemistry/genetics ; Deoxyribonuclease I/metabolism ; Early Growth Response Protein 1/genetics/metabolism ; Evolution, Molecular ; *Genome, Human ; Humans ; Mutant Proteins/metabolism ; Nucleic Acid Conformation ; Phenotype ; Polymorphism, Single Nucleotide ; Selection, Genetic
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vinson, Valda J -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):197. doi: 10.1126/science.324.5924.197.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359575" target="_blank"〉PubMed〈/a〉
    Keywords: Evolution, Molecular ; Motion ; Protein Conformation ; Proteins/*chemistry/*physiology ; Signal Transduction ; Thermodynamics
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  • 3
    Publication Date: 2009-12-08
    Description: Hepatitis delta virus (HDV) and cytoplasmic polyadenylation element-binding protein 3 (CPEB3) ribozymes form a family of self-cleaving RNAs characterized by a conserved nested double-pseudoknot and minimal sequence conservation. Secondary structure-based searches were used to identify sequences capable of forming this fold, and their self-cleavage activity was confirmed in vitro. Active sequences were uncovered in several marine organisms, two nematodes, an arthropod, a bacterium, and an insect virus, often in multiple sequence families and copies. Sequence searches based on identified ribozymes showed that plants, fungi, and a unicellular eukaryote also harbor the ribozymes. In Anopheles gambiae, the ribozymes were found differentially expressed and self-cleaved at basic developmental stages. Our results indicate that HDV-like ribozymes are abundant in nature and suggest that self-cleaving RNAs may play a variety of biological roles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159031/" 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/PMC3159031/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Webb, Chiu-Ho T -- Riccitelli, Nathan J -- Ruminski, Dana J -- Luptak, Andrej -- R01 GM094929/GM/NIGMS NIH HHS/ -- R01 GM094929-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):953. doi: 10.1126/science.1178084.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965505" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/enzymology/*genetics/growth & development ; Base Sequence ; Catalysis ; Eukaryota/enzymology/*genetics ; Expressed Sequence Tags ; Hepatitis Delta Virus/enzymology/genetics ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Catalytic/*chemistry/*metabolism
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  • 4
    Publication Date: 2009-07-18
    Description: Amino acid, polyamine, and organocation (APC) transporters are secondary transporters that play essential roles in nutrient uptake, neurotransmitter recycling, ionic homeostasis, and regulation of cell volume. Here, we present the crystal structure of apo-ApcT, a proton-coupled broad-specificity amino acid transporter, at 2.35 angstrom resolution. The structure contains 12 transmembrane helices, with the first 10 consisting of an inverted structural repeat of 5 transmembrane helices like the leucine transporter LeuT. The ApcT structure reveals an inward-facing, apo state and an amine moiety of lysine-158 located in a position equivalent to the sodium ion site Na2 of LeuT. We propose that lysine-158 is central to proton-coupled transport and that the amine group serves the same functional role as the Na2 ion in LeuT, thus demonstrating common principles among proton- and sodium-coupled transporters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851542/" 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/PMC2851542/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaffer, Paul L -- Goehring, April -- Shankaranarayanan, Aruna -- Gouaux, Eric -- R01 MH070039/MH/NIMH NIH HHS/ -- R01 MH070039-05/MH/NIMH NIH HHS/ -- T32 GM008281/GM/NIGMS NIH HHS/ -- T32 GM008281-17/GM/NIGMS NIH HHS/ -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM075026-040002/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1010-4. doi: 10.1126/science.1176088. Epub 2009 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608859" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Transport Systems/*chemistry/*metabolism ; Amino Acids/metabolism ; Antiporters/chemistry ; Apoproteins/chemistry/metabolism ; Archaeal Proteins/*chemistry/*metabolism ; Crystallization ; Crystallography, X-Ray ; Escherichia coli Proteins/chemistry ; Methanococcus/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protons ; Sodium/metabolism ; Substrate Specificity
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  • 5
    Publication Date: 2009-05-30
    Description: Transcribing RNA polymerases oscillate between three stable states, two of which, pre- and posttranslocated, were previously subjected to x-ray crystal structure determination. We report here the crystal structure of RNA polymerase II in the third state, the reverse translocated, or "backtracked" state. The defining feature of the backtracked structure is a binding site for the first backtracked nucleotide. This binding site is occupied in case of nucleotide misincorporation in the RNA or damage to the DNA, and is termed the "P" site because it supports proofreading. The predominant mechanism of proofreading is the excision of a dinucleotide in the presence of the elongation factor SII (TFIIS). Structure determination of a cocrystal with TFIIS reveals a rearrangement whereby cleavage of the RNA may take place.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718261/" 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/PMC2718261/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Dong -- Bushnell, David A -- Huang, Xuhui -- Westover, Kenneth D -- Levitt, Michael -- Kornberg, Roger D -- GM036559/GM/NIGMS NIH HHS/ -- GM041455/GM/NIGMS NIH HHS/ -- GM049985/GM/NIGMS NIH HHS/ -- K99 GM085136/GM/NIGMS NIH HHS/ -- K99 GM085136-01/GM/NIGMS NIH HHS/ -- R00 GM085136/GM/NIGMS NIH HHS/ -- R01 GM036659/GM/NIGMS NIH HHS/ -- R01 GM041455/GM/NIGMS NIH HHS/ -- R01 GM049985/GM/NIGMS NIH HHS/ -- R01 GM049985-16/GM/NIGMS NIH HHS/ -- R37 GM036659/GM/NIGMS NIH HHS/ -- R37 GM036659-22/GM/NIGMS NIH HHS/ -- R37 GM041455/GM/NIGMS NIH HHS/ -- R37 GM041455-20/GM/NIGMS NIH HHS/ -- U54 GM072970/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 May 29;324(5931):1203-6. doi: 10.1126/science.1168729.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478184" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pair Mismatch ; Crystallography, X-Ray ; Guanosine Monophosphate/chemistry/metabolism ; Models, Molecular ; Nucleic Acid Conformation ; Oligoribonucleotides/chemistry/*metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/chemistry/*metabolism ; RNA Polymerase II/*chemistry/*metabolism ; Saccharomyces cerevisiae/*enzymology ; *Transcription, Genetic ; Transcriptional Elongation Factors/chemistry/*metabolism
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  • 6
    Publication Date: 2009-03-17
    Description: Once all chromosomes are connected to the mitotic spindle (bioriented), anaphase is initiated by the protein ubiquitylation activity of the anaphase-promoting complex/cyclosome (APC/C) and its coactivator Cdc20 (APC/C(Cdc20)). Before chromosome biorientation, anaphase is delayed by a mitotic checkpoint complex (MCC) that inhibits APC/C(Cdc20). We used single-particle electron microscopy to obtain three-dimensional models of human APC/C in various functional states: bound to MCC, to Cdc20, or to neither (apo-APC/C). These experiments revealed that MCC associates with the Cdc20 binding site on APC/C, locks the otherwise flexible APC/C in a "closed" state, and prevents binding and ubiquitylation of a wide range of different APC/C substrates. These observations clarify the structural basis for the inhibition of APC/C by spindle checkpoint proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989460/" 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/PMC2989460/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herzog, Franz -- Primorac, Ivana -- Dube, Prakash -- Lenart, Peter -- Sander, Bjorn -- Mechtler, Karl -- Stark, Holger -- Peters, Jan-Michael -- F 3407/Austrian Science Fund FWF/Austria -- New York, N.Y. -- Science. 2009 Mar 13;323(5920):1477-81. doi: 10.1126/science.1163300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19286556" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; Anaphase-Promoting Complex-Cyclosome ; Cdc20 Proteins ; Cell Cycle Proteins/chemistry/metabolism ; HeLa Cells ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Microscopy, Electron ; *Mitosis ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; Spindle Apparatus/*metabolism ; Ubiquitin-Conjugating Enzymes/chemistry/metabolism ; Ubiquitin-Protein Ligase Complexes/*chemistry/*metabolism ; Ubiquitination
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  • 7
    Publication Date: 2009-05-09
    Description: Despite tremendous progress in understanding the nature of the immune system, the full diversity of an organism's antibody repertoire is unknown. We used high-throughput sequencing of the variable domain of the antibody heavy chain from 14 zebrafish to analyze VDJ usage and antibody sequence. Zebrafish were found to use between 50 and 86% of all possible VDJ combinations and shared a similar frequency distribution, with some correlation of VDJ patterns between individuals. Zebrafish antibodies retained a few thousand unique heavy chains that also exhibited a shared frequency distribution. We found evidence of convergence, in which different individuals made the same antibody. This approach provides insight into the breadth of the expressed antibody repertoire and immunological diversity at the level of an individual organism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086368/" 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/PMC3086368/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinstein, Joshua A -- Jiang, Ning -- White, Richard A 3rd -- Fisher, Daniel S -- Quake, Stephen R -- DP1 OD000251/OD/NIH HHS/ -- DP1 OD000251-04/OD/NIH HHS/ -- DP1 OD000251-05/OD/NIH HHS/ -- DP1 OD000251-06/OD/NIH HHS/ -- New York, N.Y. -- Science. 2009 May 8;324(5928):807-10. doi: 10.1126/science.1170020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Program, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423829" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/genetics ; Antibody Diversity ; Base Sequence ; Complementarity Determining Regions/*genetics ; Computational Biology ; Female ; Gene Library ; *Genes, Immunoglobulin Heavy Chain ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Joining Region/genetics ; Immunoglobulin M/*genetics ; Male ; Molecular Sequence Data ; Recombination, Genetic ; Sequence Analysis, DNA ; VDJ Exons ; Zebrafish/genetics/*immunology
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  • 8
    Publication Date: 2009-03-28
    Description: P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of approximately 6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052/" 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/PMC2720052/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aller, Stephen G -- Yu, Jodie -- Ward, Andrew -- Weng, Yue -- Chittaboina, Srinivas -- Zhuo, Rupeng -- Harrell, Patina M -- Trinh, Yenphuong T -- Zhang, Qinghai -- Urbatsch, Ina L -- Chang, Geoffrey -- F32 GM078914/GM/NIGMS NIH HHS/ -- F32 GM078914-03/GM/NIGMS NIH HHS/ -- GM073197/GM/NIGMS NIH HHS/ -- GM078914/GM/NIGMS NIH HHS/ -- GM61905/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-050002/GM/NIGMS NIH HHS/ -- R01 GM061905/GM/NIGMS NIH HHS/ -- R01 GM061905-09/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1718-22. doi: 10.1126/science.1168750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325113" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Apoproteins/chemistry/metabolism ; Binding Sites ; Cell Membrane/chemistry ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers/chemistry ; Mice ; Models, Molecular ; Molecular Sequence Data ; P-Glycoprotein/antagonists & inhibitors/*chemistry/*metabolism ; Peptides, Cyclic/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Stereoisomerism ; Verapamil/metabolism/pharmacology
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  • 9
    Publication Date: 2009-03-03
    Description: Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in maintaining small RNA-associated gene silencing. Curiously, the eudicot Arabidopsis thaliana is not affected when either function is lost. By use of mutation selection and positional cloning, we showed that the largest subunit of the presumed maize Pol IV is involved in paramutation, an inherited epigenetic change facilitated by an interaction between two alleles, as well as normal maize development. Bioinformatics analyses and nuclear run-on transcription assays indicate that Pol IV does not engage in the efficient RNA synthesis typical of the three major eukaryotic DNA-dependent RNA polymerases. These results indicate that Pol IV employs abnormal RNA polymerase activities to achieve genome-wide silencing and that its absence affects both maize development and heritable epigenetic changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erhard, Karl F Jr -- Stonaker, Jennifer L -- Parkinson, Susan E -- Lim, Jana P -- Hale, Christopher J -- Hollick, Jay B -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1201-5. doi: 10.1126/science.1164508.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant and Microbial Biology, 111 Koshland Hall, University of California, Berkeley, CA 94720-3102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251626" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Computational Biology ; DNA-Directed RNA Polymerases/chemistry/genetics/*metabolism ; *Epigenesis, Genetic ; Gene Silencing ; Genes, Plant ; Molecular Sequence Data ; *Mutation ; Phylogeny ; Protein Subunits/chemistry/genetics/metabolism ; RNA, Plant/genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; Transcription, Genetic ; Zea mays/*enzymology/*genetics/growth & development
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  • 10
    Publication Date: 2009-04-18
    Description: Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777810/" 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/PMC2777810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meijsing, Sebastiaan H -- Pufall, Miles A -- So, Alex Y -- Bates, Darren L -- Chen, Lin -- Yamamoto, Keith R -- GM08537/GM/NIGMS NIH HHS/ -- R01 CA020535/CA/NCI NIH HHS/ -- R01 CA020535-31/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):407-10. doi: 10.1126/science.1164265.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19372434" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Crystallography, X-Ray ; DNA/*chemistry/*metabolism ; Humans ; Ligands ; Models, Molecular ; Mutation ; Protein Conformation ; Protein Isoforms/chemistry/metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Receptors, Glucocorticoid/chemistry/genetics/*metabolism ; Transcriptional Activation
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  • 11
    Publication Date: 2009-12-08
    Description: Primordial organisms of the putative RNA world would have required polymerase ribozymes able to replicate RNA. Known ribozymes with polymerase activity best approximating that needed for RNA replication contain at their catalytic core the class I RNA ligase, an artificial ribozyme with a catalytic rate among the fastest of known ribozymes. Here we present the 3.0 angstrom crystal structure of this ligase. The architecture resembles a tripod, its three legs converging near the ligation junction. Interacting with this tripod scaffold through a series of 10 minor-groove interactions (including two A-minor triads) is the unpaired segment that contributes to and organizes the active site. A cytosine nucleobase and two backbone phosphates abut the ligation junction; their location suggests a model for catalysis resembling that of proteinaceous polymerases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978776/" 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/PMC3978776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shechner, David M -- Grant, Robert A -- Bagby, Sarah C -- Koldobskaya, Yelena -- Piccirilli, Joseph A -- Bartel, David P -- GM61835/GM/NIGMS NIH HHS/ -- R01 GM061835/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1271-5. doi: 10.1126/science.1174676.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965478" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalysis ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/chemistry/metabolism ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Magnesium/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Polynucleotide Ligases/chemistry/metabolism ; RNA, Catalytic/*chemistry/metabolism ; Ribonucleotides/chemistry/metabolism
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  • 12
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sheps, Jonathan A -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1679-80. doi: 10.1126/science.1172428.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genetics and Developmental Biology, BC Cancer Research Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3 Canada. jsheps@bccrc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325102" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Biological Transport ; Crystallography, X-Ray ; Drug Design ; Lipid Bilayers/chemistry ; Models, Biological ; Oligopeptides/chemistry/metabolism ; P-Glycoprotein/*chemistry/*metabolism ; Peptides, Cyclic/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Stereoisomerism
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  • 13
    Publication Date: 2009-05-16
    Description: Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905877/" 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/PMC2905877/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Badis, Gwenael -- Berger, Michael F -- Philippakis, Anthony A -- Talukder, Shaheynoor -- Gehrke, Andrew R -- Jaeger, Savina A -- Chan, Esther T -- Metzler, Genita -- Vedenko, Anastasia -- Chen, Xiaoyu -- Kuznetsov, Hanna -- Wang, Chi-Fong -- Coburn, David -- Newburger, Daniel E -- Morris, Quaid -- Hughes, Timothy R -- Bulyk, Martha L -- R01 HG003985/HG/NHGRI NIH HHS/ -- R01 HG003985-01/HG/NHGRI NIH HHS/ -- R01 HG003985-02/HG/NHGRI NIH HHS/ -- R01 HG003985-03/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1720-3. doi: 10.1126/science.1162327. Epub 2009 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443739" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/chemistry/*metabolism ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Mice ; Protein Array Analysis ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Transcription Factors/*chemistry/*metabolism
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  • 14
    Publication Date: 2009-09-12
    Description: Miniature inverted repeat transposable elements (MITEs) are widespread in eukaryotic genomes, where they can attain high copy numbers despite a lack of coding capacity. However, little is known about how they originate and amplify. We performed a genome-wide screen of functional interactions between Stowaway MITEs and potential transposases in the rice genome and identified a transpositionally active MITE that possesses key properties that enhance transposition. Although not directly related to its autonomous element, the MITE has less affinity for the transposase than does the autonomous element but lacks a motif repressing transposition in the autonomous element. The MITE contains internal sequences that enhance transposition. These findings suggest that MITEs achieve high transposition activity by scavenging transposases encoded by distantly related and self-restrained autonomous elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Guojun -- Nagel, Dawn Holligan -- Feschotte, Cedric -- Hancock, C Nathan -- Wessler, Susan R -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1391-4. doi: 10.1126/science.1175688.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, University of Georgia, Athens, GA 30602, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745152" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA Transposable Elements ; *Genome, Plant ; Inverted Repeat Sequences ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oryza/*genetics/metabolism ; Transposases/genetics/*metabolism
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  • 15
    Publication Date: 2009-01-10
    Description: Type IV secretion systems (T4SSs) are important virulence factors used by Gram-negative bacterial pathogens to inject effectors into host cells or to spread plasmids harboring antibiotic resistance genes. We report the 15 angstrom resolution cryo-electron microscopy structure of the core complex of a T4SS. The core complex is composed of three proteins, each present in 14 copies and forming a approximately 1.1-megadalton two-chambered, double membrane-spanning channel. The structure is double-walled, with each component apparently spanning a large part of the channel. The complex is open on the cytoplasmic side and constricted on the extracellular side. Overall, the T4SS core complex structure is different in both architecture and composition from the other known double membrane-spanning secretion system that has been structurally characterized.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fronzes, Remi -- Schafer, Eva -- Wang, Luchun -- Saibil, Helen R -- Orlova, Elena V -- Waksman, Gabriel -- 070776/Wellcome Trust/United Kingdom -- BB/C516144/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C516179/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F010281/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):266-8. doi: 10.1126/science.1166101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Structural and Molecular Biology, School of Crystallography, Birkbeck College, Malet Street, London, WC1E 7HX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131631" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*chemistry/genetics/ultrastructure ; Bacterial Proteins/*chemistry/genetics/*ultrastructure ; Cloning, Molecular ; Cryoelectron Microscopy ; Gram-Negative Bacteria/*chemistry/genetics/pathogenicity ; Imaging, Three-Dimensional ; Models, Molecular ; Multiprotein Complexes/chemistry/ultrastructure ; *Plasmids ; Protein Conformation ; Protein Structure, Quaternary ; Virulence Factors/*chemistry/genetics
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  • 16
    Publication Date: 2009-09-26
    Description: To explore the mechanisms and evolution of cell-cycle control, we analyzed the position and conservation of large numbers of phosphorylation sites for the cyclin-dependent kinase Cdk1 in the budding yeast Saccharomyces cerevisiae. We combined specific chemical inhibition of Cdk1 with quantitative mass spectrometry to identify the positions of 547 phosphorylation sites on 308 Cdk1 substrates in vivo. Comparisons of these substrates with orthologs throughout the ascomycete lineage revealed that the position of most phosphorylation sites is not conserved in evolution; instead, clusters of sites shift position in rapidly evolving disordered regions. We propose that the regulation of protein function by phosphorylation often depends on simple nonspecific mechanisms that disrupt or enhance protein-protein interactions. The gain or loss of phosphorylation sites in rapidly evolving regions could facilitate the evolution of kinase-signaling circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813701/" 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/PMC2813701/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holt, Liam J -- Tuch, Brian B -- Villen, Judit -- Johnson, Alexander D -- Gygi, Steven P -- Morgan, David O -- GM037049/GM/NIGMS NIH HHS/ -- GM50684/GM/NIGMS NIH HHS/ -- HG3456/HG/NHGRI NIH HHS/ -- R01 GM069901/GM/NIGMS NIH HHS/ -- R01 GM069901-06/GM/NIGMS NIH HHS/ -- R01 HG003456/HG/NHGRI NIH HHS/ -- R01 HG003456-06/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 25;325(5948):1682-6. doi: 10.1126/science.1172867.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Physiology and Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779198" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Ascomycota/chemistry/genetics/metabolism ; *Biological Evolution ; CDC2 Protein Kinase/antagonists & inhibitors/*metabolism ; *Cell Cycle ; Cell Physiological Processes ; Computational Biology ; *Evolution, Molecular ; Molecular Sequence Data ; Phosphopeptides/chemistry/*metabolism ; Phosphorylation ; Phylogeny ; Protein Conformation ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; *Signal Transduction ; Substrate Specificity
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  • 17
    Publication Date: 2009-12-08
    Description: Although the nematode Caenorhabditis elegans produces self-fertile hermaphrodites, it descended from a male/female species, so hermaphroditism provides a model for the origin of novel traits. In the related species C. remanei, which has only male and female sexes, lowering the activity of tra-2 by RNA interference created XX animals that made spermatids as well as oocytes, but their spermatids could not activate without the addition of male seminal fluid. However, by lowering the expression of both tra-2 and swm-1, a gene that regulates sperm activation in C. elegans, we produced XX animals with active sperm that were self-fertile. Thus, the evolution of hermaphroditism in Caenorhabditis probably required two steps: a mutation in the sex-determination pathway that caused XX spermatogenesis and a mutation that allowed these spermatids to self-activate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldi, Chris -- Cho, Soochin -- Ellis, Ronald E -- New York, N.Y. -- Science. 2009 Nov 13;326(5955):1002-5. doi: 10.1126/science.1176013.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Caenorhabditis/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans/anatomy & histology/classification/*genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Crosses, Genetic ; Disorders of Sex Development/genetics ; Female ; Genes, Helminth ; Germ Cells/physiology ; Male ; Membrane Proteins/genetics/physiology ; Molecular Sequence Data ; *Mutation ; Oogenesis ; Ovulation ; Phylogeny ; Reproduction ; Selection, Genetic ; Sex Determination Processes ; Spermatids/physiology ; Spermatogenesis
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  • 18
    Publication Date: 2009-09-04
    Description: The Hedgehog (Hh) signaling pathway is inappropriately activated in certain human cancers, including medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that inhibits Hh signaling by targeting the serpentine receptor Smoothened (SMO), has produced promising anti-tumor responses in early clinical studies of cancers driven by mutations in this pathway. To evaluate the mechanism of resistance in a medulloblastoma patient who had relapsed after an initial response to GDC-0449, we determined the mutational status of Hh signaling genes in the tumor after disease progression. We identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway. A mutation altering the same amino acid also arose in a GDC-0449-resistant mouse model of medulloblastoma. These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yauch, Robert L -- Dijkgraaf, Gerrit J P -- Alicke, Bruno -- Januario, Thomas -- Ahn, Christina P -- Holcomb, Thomas -- Pujara, Kanan -- Stinson, Jeremy -- Callahan, Christopher A -- Tang, Tracy -- Bazan, J Fernando -- Kan, Zhengyan -- Seshagiri, Somasekar -- Hann, Christine L -- Gould, Stephen E -- Low, Jennifer A -- Rudin, Charles M -- de Sauvage, Frederic J -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):572-4. doi: 10.1126/science.1179386. Epub 2009 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19726788" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Anilides/metabolism/pharmacology/*therapeutic use ; Animals ; Antineoplastic Agents/metabolism/pharmacology/*therapeutic use ; Brain Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cinnamates/pharmacology ; Drug Resistance, Neoplasm ; Hedgehog Proteins/antagonists & inhibitors/genetics/*metabolism ; Humans ; Medulloblastoma/*drug therapy/*genetics/pathology ; Mice ; Molecular Sequence Data ; Mutant Proteins/antagonists & inhibitors/chemistry/metabolism ; Mutation, Missense ; Neoplasm Metastasis ; Protein Conformation ; Pyridines/metabolism/pharmacology/*therapeutic use ; Receptors, Cell Surface/genetics/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/chemistry/*genetics/metabolism ; Signal Transduction ; Veratrum Alkaloids/pharmacology
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  • 19
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-15
    Description: Dynamin-related proteins (DRPs) can generate forces to remodel membranes. In cells, DRPs require additional proteins [DRP-associated proteins (DAPs)] to conduct their functions. To dissect the mechanistic role of a DAP, we used the yeast mitochondrial division machine as a model, which requires the DRP Dnm1, and two other proteins, Mdv1 and Fis1. Mdv1 played a postmitochondrial targeting role in division by specifically interacting and coassembling with the guanosine triphosphate-bound form of Dnm1. This regulated interaction nucleated and promoted the self-assembly of Dnm1 into helical structures, which drive membrane scission. The nucleation of DRP assembly probably represents a general regulatory strategy for this family of filament-forming proteins, similar to F-actin regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lackner, Laura L -- Horner, Jennifer S -- Nunnari, Jodi -- 1F32GM078749/GM/NIGMS NIH HHS/ -- R01 GM062942/GM/NIGMS NIH HHS/ -- R01GM062942/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 14;325(5942):874-7. doi: 10.1126/science.1176921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19679814" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*metabolism ; GTP Phosphohydrolases/chemistry/genetics/*metabolism ; Guanosine Triphosphate/analogs & derivatives/metabolism ; Intracellular Membranes/physiology ; Kinetics ; Liposomes/metabolism ; Mitochondria/*physiology ; Mitochondrial Proteins/chemistry/genetics/*metabolism ; Models, Biological ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
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  • 20
    Publication Date: 2009-04-25
    Description: Polyphosphate (polyP) occurs ubiquitously in cells, but its functions are poorly understood and its synthesis has only been characterized in bacteria. Using x-ray crystallography, we identified a eukaryotic polyphosphate polymerase within the membrane-integral vacuolar transporter chaperone (VTC) complex. A 2.6 angstrom crystal structure of the catalytic domain grown in the presence of adenosine triphosphate (ATP) reveals polyP winding through a tunnel-shaped pocket. Nucleotide- and phosphate-bound structures suggest that the enzyme functions by metal-assisted cleavage of the ATP gamma-phosphate, which is then in-line transferred to an acceptor phosphate to form polyP chains. Mutational analysis of the transmembrane domain indicates that VTC may integrate cytoplasmic polymer synthesis with polyP membrane translocation. Identification of the polyP-synthesizing enzyme opens the way to determine the functions of polyP in lower eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hothorn, Michael -- Neumann, Heinz -- Lenherr, Esther D -- Wehner, Mark -- Rybin, Vladimir -- Hassa, Paul O -- Uttenweiler, Andreas -- Reinhardt, Monique -- Schmidt, Andrea -- Seiler, Jeanette -- Ladurner, Andreas G -- Herrmann, Christian -- Scheffzek, Klaus -- Mayer, Andreas -- G0500367/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):513-6. doi: 10.1126/science.1168120.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Structural and Computational Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390046" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport ; Catalysis ; Catalytic Domain ; Crystallography, X-Ray ; Membrane Proteins/*chemistry/metabolism ; Models, Molecular ; Phosphotransferases/*chemistry/metabolism ; Polyphosphates/*chemistry/metabolism ; Protein Conformation ; Saccharomyces cerevisiae/enzymology/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism
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  • 21
    Publication Date: 2009-10-17
    Description: Elongation factor G (EF-G) is a guanosine triphosphatase (GTPase) that plays a crucial role in the translocation of transfer RNAs (tRNAs) and messenger RNA (mRNA) during translation by the ribosome. We report a crystal structure refined to 3.6 angstrom resolution of the ribosome trapped with EF-G in the posttranslocational state using the antibiotic fusidic acid. Fusidic acid traps EF-G in a conformation intermediate between the guanosine triphosphate and guanosine diphosphate forms. The interaction of EF-G with ribosomal elements implicated in stimulating catalysis, such as the L10-L12 stalk and the L11 region, and of domain IV of EF-G with the tRNA at the peptidyl-tRNA binding site (P site) and with mRNA shed light on the role of these elements in EF-G function. The stabilization of the mobile stalks of the ribosome also results in a more complete description of its structure.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763468/" 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/PMC3763468/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Yong-Gui -- Selmer, Maria -- Dunham, Christine M -- Weixlbaumer, Albert -- Kelley, Ann C -- Ramakrishnan, V -- 082086/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Oct 30;326(5953):694-9. doi: 10.1126/science.1179709.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833919" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry ; Catalysis ; Crystallography, X-Ray ; Fusidic Acid/chemistry/pharmacology ; Models, Molecular ; Peptide Elongation Factor G/*chemistry ; Protein Biosynthesis ; Protein Conformation ; Protein Structure, Tertiary ; Protein Synthesis Inhibitors/chemistry/pharmacology ; RNA, Bacterial/chemistry ; RNA, Messenger/chemistry ; RNA, Transfer/chemistry ; Ribosomes/*chemistry ; Thermus thermophilus
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  • 22
    Publication Date: 2009-05-30
    Description: Virulent enteric pathogens such as Escherichia coli strain O157:H7 rely on acid-resistance (AR) systems to survive the acidic environment in the stomach. A major component of AR is an arginine-dependent arginine:agmatine antiporter that expels intracellular protons. Here, we report the crystal structure of AdiC, the arginine:agmatine antiporter from E. coli O157:H7 and a member of the amino acid/polyamine/organocation (APC) superfamily of transporters at 3.6 A resolution. The overall fold is similar to that of several Na+-coupled symporters. AdiC contains 12 transmembrane segments, forms a homodimer, and exists in an outward-facing, open conformation in the crystals. A conserved, acidic pocket opens to the periplasm. Structural and biochemical analysis reveals the essential ligand-binding residues, defines the transport route, and suggests a conserved mechanism for the antiporter activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Xiang -- Lu, Feiran -- Zhou, Lijun -- Dang, Shangyu -- Sun, Linfeng -- Li, Xiaochun -- Wang, Jiawei -- Shi, Yigong -- New York, N.Y. -- Science. 2009 Jun 19;324(5934):1565-8. doi: 10.1126/science.1173654. Epub 2009 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478139" target="_blank"〉PubMed〈/a〉
    Keywords: Agmatine/metabolism ; Amino Acid Sequence ; Amino Acid Transport Systems/*chemistry/genetics/metabolism/physiology ; Antiporters/*chemistry/genetics/metabolism/physiology ; Arginine/metabolism ; Conserved Sequence ; Crystallography, X-Ray ; Escherichia coli O157/*chemistry/genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/metabolism/physiology ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation
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  • 23
    Publication Date: 2009-11-07
    Description: The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate-activated protein kinase (AMPK). LKB1 activity is regulated by the pseudokinase STRADalpha and the scaffolding protein MO25alpha through an unknown, phosphorylation-independent, mechanism. We describe the structure of the core heterotrimeric LKB1-STRADalpha-MO25alpha complex, revealing an unusual allosteric mechanism of LKB1 activation. STRADalpha adopts a closed conformation typical of active protein kinases and binds LKB1 as a pseudosubstrate. STRADalpha and MO25alpha promote the active conformation of LKB1, which is stabilized by MO25alpha interacting with the LKB1 activation loop. This previously undescribed mechanism of kinase activation may be relevant to understanding the evolution of other pseudokinases. The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518268/" 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/PMC3518268/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zeqiraj, Elton -- Filippi, Beatrice Maria -- Deak, Maria -- Alessi, Dario R -- van Aalten, Daan M F -- 087590/Wellcome Trust/United Kingdom -- C33794/A10969/Cancer Research UK/United Kingdom -- G0900138/Medical Research Council/United Kingdom -- MC_U127070193/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1707-11. doi: 10.1126/science.1178377. Epub 2009 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892943" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; Adaptor Proteins, Vesicular Transport/*chemistry/metabolism ; Allosteric Regulation ; Amino Acid Sequence ; Binding Sites ; Calcium-Binding Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; Models, Molecular ; Molecular Sequence Data ; Multiprotein Complexes/chemistry/metabolism ; Mutant Proteins/chemistry/metabolism ; Mutation ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/*chemistry/metabolism
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gebhardt, J Christof M -- Rief, Matthias -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1278-80. doi: 10.1126/science.1175874.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physik Department E22, Technische Universitat Munchen, James-Franck-Strasse, 85748 Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498156" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins/*metabolism ; Binding Sites ; Blood Coagulation/physiology ; Hemostasis/*physiology ; Humans ; *Mechanical Phenomena ; Optical Tweezers ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Tertiary ; Stress, Mechanical ; von Willebrand Factor/*chemistry/*metabolism
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  • 25
    Publication Date: 2009-01-31
    Description: The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that alpha(5)beta(1) integrin switches between relaxed and tensioned states in response to myosin II-generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers the integrin switch. This switch directly controls the alpha(5)beta(1)-fibronectin bond strength through engaging the synergy site in fibronectin and is required to generate signals through phosphorylation of focal adhesion kinase. In the context of tissues, this integrin switch connects cytoskeleton and extracellular matrix mechanics to adhesion-dependent motility and signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedland, Julie C -- Lee, Mark H -- Boettiger, David -- GM57388/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):642-4. doi: 10.1126/science.1168441.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179533" target="_blank"〉PubMed〈/a〉
    Keywords: Actins ; Biophysical Phenomena ; Cell Adhesion ; Cell Line, Tumor ; Cytoskeleton/*physiology ; Fibronectins/chemistry/*metabolism ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Humans ; Integrin alpha5beta1/*chemistry/*metabolism ; Ligands ; Models, Molecular ; Myosin Type II/antagonists & inhibitors/metabolism ; Phosphorylation ; Protein Binding ; Protein Conformation ; Signal Transduction
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  • 26
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-01-24
    Description: The two universally required components of the intracellular membrane fusion machinery, SNARE and SM (Sec1/Munc18-like) proteins, play complementary roles in fusion. Vesicular and target membrane-localized SNARE proteins zipper up into an alpha-helical bundle that pulls the two membranes tightly together to exert the force required for fusion. SM proteins, shaped like clasps, bind to trans-SNARE complexes to direct their fusogenic action. Individual fusion reactions are executed by distinct combinations of SNARE and SM proteins to ensure specificity, and are controlled by regulators that embed the SM-SNARE fusion machinery into a physiological context. This regulation is spectacularly apparent in the exquisite speed and precision of synaptic exocytosis, where synaptotagmin (the calcium-ion sensor for fusion) cooperates with complexin (the clamp activator) to control the precisely timed release of neurotransmitters that initiates synaptic transmission and underlies brain function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736821/" 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/PMC3736821/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sudhof, Thomas C -- Rothman, James E -- R01 GM071458/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jan 23;323(5913):474-7. doi: 10.1126/science.1161748.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Physiology, Stanford University, Palo Alto, CA 94304, USA. tcs1@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19164740" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; *Membrane Fusion ; Munc18 Proteins/chemistry/*metabolism ; Nerve Tissue Proteins/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Qa-SNARE Proteins/chemistry/metabolism ; SNARE Proteins/chemistry/*metabolism ; Synapses/physiology ; Synaptic Transmission ; Synaptic Vesicles/physiology ; Synaptotagmins/metabolism ; Vesicular Transport Proteins/chemistry/*metabolism
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  • 27
    Publication Date: 2009-09-19
    Description: Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima. The network encompassed 478 proteins, of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse but mostly related functions. Most of these folds are already present in the essential core (approximately 30%) of the network, and its expansion by nonessential proteins is achieved with relatively few additional folds. Thus, integration of structural data with networks analysis generates insight into the function, mechanism, and evolution of biological networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833182/" 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/PMC2833182/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ying -- Thiele, Ines -- Weekes, Dana -- Li, Zhanwen -- Jaroszewski, Lukasz -- Ginalski, Krzysztof -- Deacon, Ashley M -- Wooley, John -- Lesley, Scott A -- Wilson, Ian A -- Palsson, Bernhard -- Osterman, Andrei -- Godzik, Adam -- P20 GM076221/GM/NIGMS NIH HHS/ -- P20 GM076221-03/GM/NIGMS NIH HHS/ -- U54 GM074898/GM/NIGMS NIH HHS/ -- U54 GM074898-05/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1544-9. doi: 10.1126/science.1174671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joint Center for Molecular Modeling (JCMM), Burnham Institute for Medical Research, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762644" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/*metabolism ; Computational Biology ; Computer Simulation ; Enzymes/*chemistry/*metabolism ; Evolution, Molecular ; Genes, Bacterial ; Genome, Bacterial ; *Metabolic Networks and Pathways ; Models, Biological ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Systems Biology ; Thermotoga maritima/chemistry/genetics/*metabolism
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-16
    Description: Integrins are transmembrane cell-adhesion molecules that carry signals from the outside to the inside of the cell and vice versa. Like other cell surface receptors, integrins signal in response to ligand binding; however, events within the cell can also regulate the affinity of integrins for ligands. This feature is important in physiological situations such as those in blood, in which cells are always in close proximity to their ligands, yet cell-ligand interactions occur only after integrin activation in response to specific external cues. This review focuses on the mechanisms whereby two key proteins, talin and the kindlins, regulate integrin activation by binding the tails of integrin-beta subunits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moser, Markus -- Legate, Kyle R -- Zent, Roy -- Fassler, Reinhard -- DK 69921/DK/NIDDK NIH HHS/ -- DK075594/DK/NIDDK NIH HHS/ -- DK65138/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):895-9. doi: 10.1126/science.1163865.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19443776" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Adhesion ; Humans ; Integrins/chemistry/*metabolism ; Ligands ; Membrane Proteins/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; Signal Transduction ; Talin/chemistry/*metabolism
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  • 29
    Publication Date: 2009-07-25
    Description: The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831805/" 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/PMC2831805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geurts, Aron M -- Cost, Gregory J -- Freyvert, Yevgeniy -- Zeitler, Bryan -- Miller, Jeffrey C -- Choi, Vivian M -- Jenkins, Shirin S -- Wood, Adam -- Cui, Xiaoxia -- Meng, Xiangdong -- Vincent, Anna -- Lam, Stephen -- Michalkiewicz, Mieczyslaw -- Schilling, Rebecca -- Foeckler, Jamie -- Kalloway, Shawn -- Weiler, Hartmut -- Menoret, Severine -- Anegon, Ignacio -- Davis, Gregory D -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Jacob, Howard J -- Buelow, Roland -- 5P01HL082798-03/HL/NHLBI NIH HHS/ -- 5U01HL066579-08/HL/NHLBI NIH HHS/ -- P01 HL082798/HL/NHLBI NIH HHS/ -- P01 HL082798-03/HL/NHLBI NIH HHS/ -- U01 HL066579/HL/NHLBI NIH HHS/ -- U01 HL066579-08/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):433. doi: 10.1126/science.1172447.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Dna ; Embryo, Mammalian ; Endodeoxyribonucleases/genetics/*metabolism ; Feasibility Studies ; Female ; *Gene Knockout Techniques ; Green Fluorescent Proteins ; Immunoglobulin M/*genetics ; Male ; *Microinjections ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; RNA, Messenger ; Rats ; *Zinc Fingers/genetics ; rab GTP-Binding Proteins/*genetics
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  • 30
    Publication Date: 2009-01-20
    Description: Combining biomolecular function with integrated circuit technology could usher in a new era of biologically enabled electronics. A key challenge has been coupling different molecular functions to specific chip locations for communication with the circuit. We used spatially confined electric fields to assemble different populations of DNA-coated nanowires to desired positions with an accuracy that enabled postassembly fabrication of contacts to each individual nanowire, with high yield and without loss of DNA function. This combination of off-chip synthesis and biofunctionalization with high-density, heterogeneous assembly and integration at the individual nanowire level points to new ways of incorporating biological functionality with silicon electronics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837912/" 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/PMC2837912/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morrow, Thomas J -- Li, Mingwei -- Kim, Jaekyun -- Mayer, Theresa S -- Keating, Christine D -- R01 EB000268/EB/NIBIB NIH HHS/ -- R01 EB000268-08/EB/NIBIB NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):352. doi: 10.1126/science.1165921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150837" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA/chemistry ; Electricity ; Electronics/*instrumentation/methods ; Nanotechnology/methods ; *Nanowires/chemistry ; Oligodeoxyribonucleotides/chemistry
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-05-09
    Description: To intercept invading microbes that threaten growth and reproduction, plants evolved a sophisticated innate immune system. Recognition of specialized pathogens is mediated by resistance proteins that function as molecular switches. Pathogen perception by these multidomain proteins seems to trigger a series of conformational changes dependent on nucleotide exchange. The activated resistance protein switches on host defenses, often culminating in the death of infected cells. Given their control over life and death, activity of these proteins requires tight regulation that involves intramolecular interactions between the various domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takken, F L W -- Tameling, W I L -- New York, N.Y. -- Science. 2009 May 8;324(5928):744-6. doi: 10.1126/science.1171666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Pathology, Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Post Office Box 94215, 1090 GE Amsterdam, the Netherlands. F.L.W.Takken@uva.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19423813" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Adenosine Triphosphate/metabolism ; Host-Pathogen Interactions ; Immunity, Innate ; Plant Diseases/*immunology ; Plant Proteins/chemistry/genetics/*metabolism ; Plants/*immunology/metabolism/*microbiology ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Signal Transduction
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  • 32
    Publication Date: 2009-01-20
    Description: Vaults are among the largest cytoplasmic ribonucleoprotein particles and are found in numerous eukaryotic species. Roles in multidrug resistance and innate immunity have been suggested, but the cellular function remains unclear. We have determined the x-ray structure of rat liver vault at 3.5 angstrom resolution and show that the cage structure consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains. Each MVP monomer folds into 12 domains: nine structural repeat domains, a shoulder domain, a cap-helix domain, and a cap-ring domain. Interactions between the 42-turn-long cap-helix domains are key to stabilizing the particle. The shoulder domain is structurally similar to a core domain of stomatin, a lipid-raft component in erythrocytes and epithelial cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanaka, Hideaki -- Kato, Koji -- Yamashita, Eiki -- Sumizawa, Tomoyuki -- Zhou, Yong -- Yao, Min -- Iwasaki, Kenji -- Yoshimura, Masato -- Tsukihara, Tomitake -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):384-8. doi: 10.1126/science.1164975.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150846" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallization ; Crystallography, X-Ray ; Dimerization ; Liver/*chemistry ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Vault Ribonucleoprotein Particles/*chemistry
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  • 33
    Publication Date: 2009-08-08
    Description: The catalytic engine of RNA interference (RNAi) is the RNA-induced silencing complex (RISC), wherein the endoribonuclease Argonaute and single-stranded small interfering RNA (siRNA) direct target mRNA cleavage. We reconstituted long double-stranded RNA- and duplex siRNA-initiated RISC activities with the use of recombinant Drosophila Dicer-2, R2D2, and Ago2 proteins. We used this core reconstitution system to purify an RNAi regulator that we term C3PO (component 3 promoter of RISC), a complex of Translin and Trax. C3PO is a Mg2+-dependent endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products. These studies establish an in vitro RNAi reconstitution system and identify C3PO as a key activator of the core RNAi machinery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855623/" 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/PMC2855623/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Ying -- Ye, Xuecheng -- Jiang, Feng -- Liang, Chunyang -- Chen, Dongmei -- Peng, Junmin -- Kinch, Lisa N -- Grishin, Nick V -- Liu, Qinghua -- AG025688/AG/NIA NIH HHS/ -- GM078163/GM/NIGMS NIH HHS/ -- GM084010/GM/NIGMS NIH HHS/ -- R01 GM078163/GM/NIGMS NIH HHS/ -- R01 GM078163-03/GM/NIGMS NIH HHS/ -- R01 GM084010/GM/NIGMS NIH HHS/ -- R01 GM084010-02/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):750-3. doi: 10.1126/science.1176325.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661431" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Argonaute Proteins ; Carrier Proteins/chemistry/genetics/isolation & purification/*metabolism ; Catalytic Domain ; Drosophila Proteins/chemistry/genetics/isolation & purification/*metabolism ; Drosophila melanogaster/chemistry/enzymology/*genetics ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; RNA Helicases/genetics/metabolism ; *RNA Interference ; RNA, Double-Stranded/chemistry/metabolism ; RNA, Small Interfering/chemistry/metabolism ; RNA-Binding Proteins/genetics/metabolism ; RNA-Induced Silencing Complex/genetics/*metabolism ; Recombinant Proteins/metabolism ; Ribonuclease III/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 34
    Publication Date: 2009-12-08
    Description: We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnable, Patrick S -- Ware, Doreen -- Fulton, Robert S -- Stein, Joshua C -- Wei, Fusheng -- Pasternak, Shiran -- Liang, Chengzhi -- Zhang, Jianwei -- Fulton, Lucinda -- Graves, Tina A -- Minx, Patrick -- Reily, Amy Denise -- Courtney, Laura -- Kruchowski, Scott S -- Tomlinson, Chad -- Strong, Cindy -- Delehaunty, Kim -- Fronick, Catrina -- Courtney, Bill -- Rock, Susan M -- Belter, Eddie -- Du, Feiyu -- Kim, Kyung -- Abbott, Rachel M -- Cotton, Marc -- Levy, Andy -- Marchetto, Pamela -- Ochoa, Kerri -- Jackson, Stephanie M -- Gillam, Barbara -- Chen, Weizu -- Yan, Le -- Higginbotham, Jamey -- Cardenas, Marco -- Waligorski, Jason -- Applebaum, Elizabeth -- Phelps, Lindsey -- Falcone, Jason -- Kanchi, Krishna -- Thane, Thynn -- Scimone, Adam -- Thane, Nay -- Henke, Jessica -- Wang, Tom -- Ruppert, Jessica -- Shah, Neha -- Rotter, Kelsi -- Hodges, Jennifer -- Ingenthron, Elizabeth -- Cordes, Matt -- Kohlberg, Sara -- Sgro, Jennifer -- Delgado, Brandon -- Mead, Kelly -- Chinwalla, Asif -- Leonard, Shawn -- Crouse, Kevin -- Collura, Kristi -- Kudrna, Dave -- Currie, Jennifer -- He, Ruifeng -- Angelova, Angelina -- Rajasekar, Shanmugam -- Mueller, Teri -- Lomeli, Rene -- Scara, Gabriel -- Ko, Ara -- Delaney, Krista -- Wissotski, Marina -- Lopez, Georgina -- Campos, David -- Braidotti, Michele -- Ashley, Elizabeth -- Golser, Wolfgang -- Kim, HyeRan -- Lee, Seunghee -- Lin, Jinke -- Dujmic, Zeljko -- Kim, Woojin -- Talag, Jayson -- Zuccolo, Andrea -- Fan, Chuanzhu -- Sebastian, Aswathy -- Kramer, Melissa -- Spiegel, Lori -- Nascimento, Lidia -- Zutavern, Theresa -- Miller, Beth -- Ambroise, Claude -- Muller, Stephanie -- Spooner, Will -- Narechania, Apurva -- Ren, Liya -- Wei, Sharon -- Kumari, Sunita -- Faga, Ben -- Levy, Michael J -- McMahan, Linda -- Van Buren, Peter -- Vaughn, Matthew W -- Ying, Kai -- Yeh, Cheng-Ting -- Emrich, Scott J -- Jia, Yi -- Kalyanaraman, Ananth -- Hsia, An-Ping -- Barbazuk, W Brad -- Baucom, Regina S -- Brutnell, Thomas P -- Carpita, Nicholas C -- Chaparro, Cristian -- Chia, Jer-Ming -- Deragon, Jean-Marc -- Estill, James C -- Fu, Yan -- Jeddeloh, Jeffrey A -- Han, Yujun -- Lee, Hyeran -- Li, Pinghua -- Lisch, Damon R -- Liu, Sanzhen -- Liu, Zhijie -- Nagel, Dawn Holligan -- McCann, Maureen C -- SanMiguel, Phillip -- Myers, Alan M -- Nettleton, Dan -- Nguyen, John -- Penning, Bryan W -- Ponnala, Lalit -- Schneider, Kevin L -- Schwartz, David C -- Sharma, Anupma -- Soderlund, Carol -- Springer, Nathan M -- Sun, Qi -- Wang, Hao -- Waterman, Michael -- Westerman, Richard -- Wolfgruber, Thomas K -- Yang, Lixing -- Yu, Yeisoo -- Zhang, Lifang -- Zhou, Shiguo -- Zhu, Qihui -- Bennetzen, Jeffrey L -- Dawe, R Kelly -- Jiang, Jiming -- Jiang, Ning -- Presting, Gernot G -- Wessler, Susan R -- Aluru, Srinivas -- Martienssen, Robert A -- Clifton, Sandra W -- McCombie, W Richard -- Wing, Rod A -- Wilson, Richard K -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1112-5. doi: 10.1126/science.1178534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Plant Genomics, Iowa State University, Ames, IA 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965430" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Centromere/genetics ; Chromosome Mapping ; Chromosomes, Plant/genetics ; Crops, Agricultural/genetics ; DNA Copy Number Variations ; DNA Methylation ; DNA Transposable Elements ; DNA, Plant/genetics ; Genes, Plant ; *Genetic Variation ; *Genome, Plant ; Inbreeding ; MicroRNAs/genetics ; Molecular Sequence Data ; Ploidies ; RNA, Plant/genetics ; Recombination, Genetic ; Retroelements ; *Sequence Analysis, DNA ; Zea mays/*genetics
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  • 35
    Publication Date: 2009-06-13
    Description: Several classes of nucleic acid analogs have been reported, but no synthetic informational polymer has yet proven responsive to selection pressures under enzyme-free conditions. Here, we introduce an oligomer family that efficiently self-assembles by means of reversible covalent anchoring of nucleobase recognition units onto simple oligo-dipeptide backbones [thioester peptide nucleic acids (tPNAs)] and undergoes dynamic sequence modification in response to changing templates in solution. The oligomers specifically self-pair with complementary tPNA strands and cross-pair with RNA and DNA in Watson-Crick fashion. Thus, tPNA combines base-pairing interactions with the side-chain functionalities of typical peptides and proteins. These characteristics might prove advantageous for the design or selection of catalytic constructs or biomaterials that are capable of dynamic sequence repair and adaptation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ura, Yasuyuki -- Beierle, John M -- Leman, Luke J -- Orgel, Leslie E -- Ghadiri, M Reza -- New York, N.Y. -- Science. 2009 Jul 3;325(5936):73-7. doi: 10.1126/science.1174577. Epub 2009 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Skaggs Institute for Chemical Biology, 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/19520909" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/chemistry ; Amino Acids/chemistry ; Base Pairing ; Base Sequence ; Biotinylation ; DNA/*chemistry ; Dipeptides/chemistry ; Models, Molecular ; Molecular Structure ; Nucleic Acid Conformation ; Oligonucleotides/chemistry ; Peptide Nucleic Acids/*chemistry ; Peptides/chemistry ; RNA/chemistry
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  • 36
    Publication Date: 2009-01-31
    Description: The molecular mechanism by which a mechanical stimulus is translated into a chemical response in biological systems is still unclear. We show that mechanical stretching of single cytoplasmic proteins can activate binding of other molecules. We used magnetic tweezers, total internal reflection fluorescence, and atomic force microscopy to investigate the effect of force on the interaction between talin, a protein that links liganded membrane integrins to the cytoskeleton, and vinculin, a focal adhesion protein that is activated by talin binding, leading to reorganization of the cytoskeleton. Application of physiologically relevant forces caused stretching of single talin rods that exposed cryptic binding sites for vinculin. Thus in the talin-vinculin system, molecular mechanotransduction can occur by protein binding after exposure of buried binding sites in the talin-vinculin system. Such protein stretching may be a more general mechanism for force transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉del Rio, Armando -- Perez-Jimenez, Raul -- Liu, Ruchuan -- Roca-Cusachs, Pere -- Fernandez, Julio M -- Sheetz, Michael P -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):638-41. doi: 10.1126/science.1162912.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, NY 10027, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179532" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Biophysical Phenomena ; Chickens ; Mechanotransduction, Cellular ; Microscopy, Fluorescence ; Models, Molecular ; Photobleaching ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry/metabolism ; Talin/*chemistry/*metabolism ; Vinculin/*chemistry/*metabolism
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  • 37
    Publication Date: 2009-06-27
    Description: Escherichia coli diacylglycerol kinase (DAGK) represents a family of integral membrane enzymes that is unrelated to all other phosphotransferases. We have determined the three-dimensional structure of the DAGK homotrimer with the use of solution nuclear magnetic resonance. The third transmembrane helix from each subunit is domain-swapped with the first and second transmembrane segments from an adjacent subunit. Each of DAGK's three active sites resembles a portico. The cornice of the portico appears to be the determinant of DAGK's lipid substrate specificity and overhangs the site of phosphoryl transfer near the water-membrane interface. Mutations to cysteine that caused severe misfolding were located in or near the active site, indicating a high degree of overlap between sites responsible for folding and for catalysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764269/" 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/PMC2764269/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Horn, Wade D -- Kim, Hak-Jun -- Ellis, Charles D -- Hadziselimovic, Arina -- Sulistijo, Endah S -- Karra, Murthy D -- Tian, Changlin -- Sonnichsen, Frank D -- Sanders, Charles R -- R01 GM047485/GM/NIGMS NIH HHS/ -- R01 GM047485-17/GM/NIGMS NIH HHS/ -- R01 GM47485/GM/NIGMS NIH HHS/ -- T32 NS007491/NS/NINDS NIH HHS/ -- T32 NS007491-09/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1726-9. doi: 10.1126/science.1171716.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556511" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Biocatalysis ; Catalytic Domain ; Cell Membrane/enzymology ; Diacylglycerol Kinase/*chemistry/metabolism ; Escherichia coli/*enzymology ; Escherichia coli Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 38
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-11
    Description: The traditional view that proteins possess absolute functional specificity and a single, fixed structure conflicts with their marked ability to adapt and evolve new functions and structures. We consider an alternative, "avant-garde view" in which proteins are conformationally dynamic and exhibit functional promiscuity. We surmise that these properties are the foundation stones of protein evolvability; they facilitate the divergence of new functions within existing folds and the evolution of entirely new folds. Packing modes of proteins also affect their evolvability, and poorly packed, disordered, and conformationally diverse proteins may exhibit high evolvability. This dynamic view of protein structure, function, and evolvability is extrapolated to describe hypothetical scenarios for the evolution of the early proteins and future research directions in the area of protein dynamism and evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tokuriki, Nobuhiko -- Tawfik, Dan S -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):203-7. doi: 10.1126/science.1169375.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359577" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; *Evolution, Molecular ; Ligands ; Models, Molecular ; Mutation ; Protein Conformation ; Protein Folding ; Proteins/*chemistry/genetics/*physiology
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  • 39
    Publication Date: 2009-09-05
    Description: Collagen IV networks are ancient proteins of basement membranes that underlie epithelia in metazoa from sponge to human. The networks provide structural integrity to tissues and serve as ligands for integrin cell-surface receptors. They are assembled by oligomerization of triple-helical protomers and are covalently crosslinked, a key reinforcement that stabilizes networks. We used Fourier-transform ion cyclotron resonance mass spectrometry and nuclear magnetic resonance spectroscopy to show that a sulfilimine bond (-S=N-) crosslinks hydroxylysine-211 and methionine-93 of adjoining protomers, a bond not previously found in biomolecules. This bond, the nitrogen analog of a sulfoxide, appears to have arisen at the divergence of sponge and cnidaria, an adaptation of the extracellular matrix in response to mechanical stress in metazoan evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876822/" 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/PMC2876822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vanacore, Roberto -- Ham, Amy-Joan L -- Voehler, Markus -- Sanders, Charles R -- Conrads, Thomas P -- Veenstra, Timothy D -- Sharpless, K Barry -- Dawson, Philip E -- Hudson, Billy G -- DC007416/DC/NIDCD NIH HHS/ -- DK065123/DK/NIDDK NIH HHS/ -- DK18381/DK/NIDDK NIH HHS/ -- GM059380/GM/NIGMS NIH HHS/ -- P01 DK065123/DK/NIDDK NIH HHS/ -- P01 DK065123-07/DK/NIDDK NIH HHS/ -- R01 DC007416/DC/NIDCD NIH HHS/ -- R01 DC007416-05/DC/NIDCD NIH HHS/ -- R01 GM059380/GM/NIGMS NIH HHS/ -- R01 GM059380-09/GM/NIGMS NIH HHS/ -- R37 DK018381/DK/NIDDK NIH HHS/ -- R37 DK018381-37/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1230-4. doi: 10.1126/science.1176811.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Nephrology, Department of Medicine and Center for Matrix Biology, Vanderbilt University, Nashville, TN 37232, USA. roberto.vanacore@vanderbilt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729652" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cattle ; Collagen Type IV/*chemistry ; Humans ; Hydroxylysine/chemistry ; Mass Spectrometry ; Methionine/chemistry ; Models, Molecular ; Molecular Sequence Data ; Nitrogen/chemistry ; Nuclear Magnetic Resonance, Biomolecular ; Physicochemical Processes ; Protein Conformation ; Protein Multimerization ; Protein Subunits/chemistry ; Sequence Alignment ; Stress, Mechanical ; Sulfur/chemistry
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  • 40
    Publication Date: 2009-04-11
    Description: In vertebrates, the readily apparent left/right (L/R) anatomical asymmetries of the internal organs can be traced to molecular events initiated at or near the time of gastrulation. However, the earliest steps of this process do not seem to be universally conserved. In particular, how this axis is first defined in chicks has remained problematic. Here we show that asymmetric cell rearrangements take place within chick embryos, creating a leftward movement of cells around the node. It is the relative displacement of cells expressing sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8) that is responsible for establishing their asymmetric expression patterns. The creation of asymmetric expression domains as a passive effect of cell movements represents an alternative strategy for breaking L/R symmetry in gene activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993078/" 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/PMC2993078/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gros, Jerome -- Feistel, Kerstin -- Viebahn, Christoph -- Blum, Martin -- Tabin, Clifford J -- R01 HD045499/HD/NICHD NIH HHS/ -- R01 HD045499-06/HD/NICHD NIH HHS/ -- R01-HD045499/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2009 May 15;324(5929):941-4. doi: 10.1126/science.1172478. Epub 2009 Apr 9.〈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/19359542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Body Patterning ; *Cell Movement ; Chick Embryo ; Fibroblast Growth Factor 8/genetics ; *Gastrulation ; *Gene Expression ; Gene Expression Profiling ; Hedgehog Proteins/genetics ; Molecular Sequence Data ; Organizers, Embryonic/*cytology/embryology/*metabolism ; Primitive Streak/*cytology/embryology/metabolism ; Swine/embryology ; Tissue Culture Techniques
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  • 41
    Publication Date: 2009-12-08
    Description: To study basic principles of transcriptome organization in bacteria, we analyzed one of the smallest self-replicating organisms, Mycoplasma pneumoniae. We combined strand-specific tiling arrays, complemented by transcriptome sequencing, with more than 252 spotted arrays. We detected 117 previously undescribed, mostly noncoding transcripts, 89 of them in antisense configuration to known genes. We identified 341 operons, of which 139 are polycistronic; almost half of the latter show decaying expression in a staircase-like manner. Under various conditions, operons could be divided into 447 smaller transcriptional units, resulting in many alternative transcripts. Frequent antisense transcripts, alternative transcripts, and multiple regulators per gene imply a highly dynamic transcriptome, more similar to that of eukaryotes than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guell, Marc -- van Noort, Vera -- Yus, Eva -- Chen, Wei-Hua -- Leigh-Bell, Justine -- Michalodimitrakis, Konstantinos -- Yamada, Takuji -- Arumugam, Manimozhiyan -- Doerks, Tobias -- Kuhner, Sebastian -- Rode, Michaela -- Suyama, Mikita -- Schmidt, Sabine -- Gavin, Anne-Claude -- Bork, Peer -- Serrano, Luis -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1268-71. doi: 10.1126/science.1176951.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation (CRG), Universitat Pompeu Fabra, Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965477" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; *Genome, Bacterial ; Molecular Sequence Data ; Mycoplasma pneumoniae/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Operon ; RNA, Antisense/genetics/metabolism ; RNA, Bacterial/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Untranslated/analysis/*genetics ; *Transcription, Genetic
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  • 42
    Publication Date: 2009-11-26
    Description: Expression of the Escherichia coli tryptophanase operon depends on ribosome stalling during translation of the upstream TnaC leader peptide, a process for which interactions between the TnaC nascent chain and the ribosomal exit tunnel are critical. We determined a 5.8 angstrom-resolution cryo-electron microscopy and single-particle reconstruction of a ribosome stalled during translation of the tnaC leader gene. The nascent chain was extended within the exit tunnel, making contacts with ribosomal components at distinct sites. Upon stalling, two conserved residues within the peptidyltransferase center adopted conformations that preclude binding of release factors. We propose a model whereby interactions within the tunnel are relayed to the peptidyltransferase center to inhibit translation. Moreover, we show that nascent chains adopt distinct conformations within the ribosomal exit tunnel.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920484/" 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/PMC2920484/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seidelt, Birgit -- Innis, C Axel -- Wilson, Daniel N -- Gartmann, Marco -- Armache, Jean-Paul -- Villa, Elizabeth -- Trabuco, Leonardo G -- Becker, Thomas -- Mielke, Thorsten -- Schulten, Klaus -- Steitz, Thomas A -- Beckmann, Roland -- GM022778/GM/NIGMS NIH HHS/ -- P41 RR005969/RR/NCRR NIH HHS/ -- P41 RR005969-19/RR/NCRR NIH HHS/ -- P41-RR05969/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1412-5. doi: 10.1126/science.1177662. Epub 2009 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Center and Center for Integrated Protein Science Munich (CIPSM), Department for Chemistry and Biochemistry, University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933110" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cryoelectron Microscopy ; Escherichia coli/*genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/*metabolism/ultrastructure ; Gene Expression Regulation, Bacterial ; Image Processing, Computer-Assisted ; Models, Biological ; Models, Molecular ; Operon ; Peptidyl Transferases/metabolism ; *Protein Biosynthesis ; Protein Conformation ; RNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Ribosomal Proteins/chemistry/metabolism/ultrastructure ; Ribosomes/*metabolism/ultrastructure ; Tryptophanase/biosynthesis/*genetics
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  • 43
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉King, David G -- Kashi, Yechezkel -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):229-30. doi: 10.1126/science.326_229.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, Southern Illinois University, Carbondale, IL 62901, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815757" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; DNA/chemistry/*genetics ; Evolution, Molecular ; Mutation ; *Repetitive Sequences, Nucleic Acid
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  • 44
    Publication Date: 2009-10-17
    Description: The ribosome selects a correct transfer RNA (tRNA) for each amino acid added to the polypeptide chain, as directed by messenger RNA. Aminoacyl-tRNA is delivered to the ribosome by elongation factor Tu (EF-Tu), which hydrolyzes guanosine triphosphate (GTP) and releases tRNA in response to codon recognition. The signaling pathway that leads to GTP hydrolysis upon codon recognition is critical to accurate decoding. Here we present the crystal structure of the ribosome complexed with EF-Tu and aminoacyl-tRNA, refined to 3.6 angstrom resolution. The structure reveals details of the tRNA distortion that allows aminoacyl-tRNA to interact simultaneously with the decoding center of the 30S subunit and EF-Tu at the factor binding site. A series of conformational changes in EF-Tu and aminoacyl-tRNA suggests a communication pathway between the decoding center and the guanosine triphosphatase center of EF-Tu.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763470/" 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/PMC3763470/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmeing, T Martin -- Voorhees, Rebecca M -- Kelley, Ann C -- Gao, Yong-Gui -- Murphy, Frank V 4th -- Weir, John R -- Ramakrishnan, V -- 082086/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Oct 30;326(5953):688-94. doi: 10.1126/science.1179700. Epub 2009 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833920" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Enzyme Activation ; GTP Phosphohydrolases/metabolism ; Genetic Code ; Models, Molecular ; Nucleic Acid Conformation ; Peptide Elongation Factor Tu/*chemistry ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Bacterial/*chemistry ; RNA, Transfer, Amino Acyl/*chemistry ; RNA, Transfer, Phe/chemistry ; RNA, Transfer, Thr/chemistry ; Ribosomes/*chemistry ; Thermus thermophilus
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  • 45
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Otterstrom, Jason J -- van Oijen, Antoine M -- R01 GM077248/GM/NIGMS NIH HHS/ -- R01 GM077248-03/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):547-8. doi: 10.1126/science.1177311.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644099" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalytic Domain ; DNA/chemistry/*metabolism ; Diffusion ; Nucleosomes/*metabolism ; Optical Tweezers ; RNA Polymerase II/chemistry/*metabolism ; RNA, Messenger/metabolism ; Templates, Genetic ; *Transcription, Genetic
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  • 46
    Publication Date: 2009-07-18
    Description: Selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA). O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) catalyzes the final step of selenocysteine formation by a poorly understood tRNA-dependent mechanism. The crystal structure of human tRNA(Sec) in complex with SepSecS, phosphoserine, and thiophosphate, together with in vivo and in vitro enzyme assays, supports a pyridoxal phosphate-dependent mechanism of Sec-tRNA(Sec) formation. Two tRNA(Sec) molecules, with a fold distinct from other canonical tRNAs, bind to each SepSecS tetramer through their 13-base pair acceptor-TPsiC arm (where Psi indicates pseudouridine). The tRNA binding is likely to induce a conformational change in the enzyme's active site that allows a phosphoserine covalently attached to tRNA(Sec), but not free phosphoserine, to be oriented properly for the reaction to occur.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857584/" 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/PMC2857584/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palioura, Sotiria -- Sherrer, R Lynn -- Steitz, Thomas A -- Soll, Dieter -- Simonovic, Miljan -- R01 GM022854/GM/NIGMS NIH HHS/ -- R01 GM022854-33/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):321-5. doi: 10.1126/science.1173755.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19608919" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/*chemistry/*metabolism ; Base Sequence ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phosphates/chemistry/metabolism ; Phosphoserine/chemistry/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; RNA, Transfer, Amino Acid-Specific/*chemistry/*metabolism ; RNA, Transfer, Amino Acyl/*metabolism ; Selenocysteine/*biosynthesis/genetics
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  • 47
    Publication Date: 2009-12-08
    Description: Previous x-ray crystal structures have given insight into the mechanism of transcription and the role of general transcription factors in the initiation of the process. A structure of an RNA polymerase II-general transcription factor TFIIB complex at 4.5 angstrom resolution revealed the amino-terminal region of TFIIB, including a loop termed the "B finger," reaching into the active center of the polymerase where it may interact with both DNA and RNA, but this structure showed little of the carboxyl-terminal region. A new crystal structure of the same complex at 3.8 angstrom resolution obtained under different solution conditions is complementary with the previous one, revealing the carboxyl-terminal region of TFIIB, located above the polymerase active center cleft, but showing none of the B finger. In the new structure, the linker between the amino- and carboxyl-terminal regions can also be seen, snaking down from above the cleft toward the active center. The two structures, taken together with others previously obtained, dispel long-standing mysteries of the transcription initiation process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813267/" 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/PMC2813267/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Xin -- Bushnell, David A -- Wang, Dong -- Calero, Guillermo -- Kornberg, Roger D -- AI21144/AI/NIAID NIH HHS/ -- GM049985/GM/NIGMS NIH HHS/ -- K99 GM085136/GM/NIGMS NIH HHS/ -- K99 GM085136-02/GM/NIGMS NIH HHS/ -- R00 GM085136/GM/NIGMS NIH HHS/ -- R01 AI021144/AI/NIAID NIH HHS/ -- R01 AI021144-25/AI/NIAID NIH HHS/ -- R01 GM036659/GM/NIGMS NIH HHS/ -- R01 GM049985/GM/NIGMS NIH HHS/ -- R01 GM049985-16/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):206-9. doi: 10.1126/science.1182015. Epub 2009 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965383" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA Polymerase II/*chemistry/*metabolism ; Repetitive Sequences, Amino Acid ; Saccharomyces cerevisiae/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism ; Transcription Factor TFIIB/*chemistry/*metabolism ; *Transcription, Genetic
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  • 48
    Publication Date: 2009-12-19
    Description: We report here crystallization at long range in networks of like-charge supramolecular peptide filaments mediated by repulsive forces. The crystallization is spontaneous beyond a given concentration of the molecules that form the filaments but can be triggered by x-rays at lower concentrations. The crystalline domains formed by x-ray irradiation, with interfilament separations of up to 320 angstroms, can be stable for hours after the beam is turned off, and ions that screen charges on the filaments suppress ordering. We hypothesize that the stability of crystalline domains emerges from a balance of repulsive tensions linked to native or x-ray-induced charges and the mechanical compressive entrapment of filaments within a network. Similar phenomena may occur naturally in the cytoskeleton of cells and, if induced externally in biological or artificial systems, lead to possible biomedical and lithographic functions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086396/" 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/PMC3086396/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cui, Honggang -- Pashuck, E Thomas -- Velichko, Yuri S -- Weigand, Steven J -- Cheetham, Andrew G -- Newcomb, Christina J -- Stupp, Samuel I -- 5R01 DE015920/DE/NIDCR NIH HHS/ -- R01 DE015920/DE/NIDCR NIH HHS/ -- R01 DE015920-05/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 29;327(5965):555-9. doi: 10.1126/science.1182340. Epub 2009 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019248" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Crystallization ; *Nanostructures/ultrastructure ; Oxygen ; Peptides/*chemistry/*radiation effects ; Physicochemical Phenomena ; Protein Conformation ; Scattering, Small Angle ; Static Electricity ; Temperature ; X-Ray Diffraction ; X-Rays
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  • 49
    Publication Date: 2009-12-08
    Description: Tetrathiomolybdate (TM) is an orally active agent for treatment of disorders of copper metabolism. Here we describe how TM inhibits proteins that regulate copper physiology. Crystallographic results reveal that the surprising stability of the drug complex with the metallochaperone Atx1 arises from formation of a sulfur-bridged copper-molybdenum cluster reminiscent of those found in molybdenum and iron sulfur proteins. Spectroscopic studies indicate that this cluster is stable in solution and corresponds to physiological clusters isolated from TM-treated Wilson's disease animal models. Finally, mechanistic studies show that the drug-metallochaperone inhibits metal transfer functions between copper-trafficking proteins. The results are consistent with a model wherein TM can directly and reversibly down-regulate copper delivery to secreted metalloenzymes and suggest that proteins involved in metal regulation might be fruitful drug targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658115/" 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/PMC3658115/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alvarez, Hamsell M -- Xue, Yi -- Robinson, Chandler D -- Canalizo-Hernandez, Monica A -- Marvin, Rebecca G -- Kelly, Rebekah A -- Mondragon, Alfonso -- Penner-Hahn, James E -- O'Halloran, Thomas V -- GM38047/GM/NIGMS NIH HHS/ -- GM38784/GM/NIGMS NIH HHS/ -- GM54222/GM/NIGMS NIH HHS/ -- R01 GM038047/GM/NIGMS NIH HHS/ -- R01 GM038784/GM/NIGMS NIH HHS/ -- R01 GM054111/GM/NIGMS NIH HHS/ -- R37 GM038784/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):331-4. doi: 10.1126/science.1179907. Epub 2009 Nov 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965379" target="_blank"〉PubMed〈/a〉
    Keywords: Carrier Proteins/*antagonists & inhibitors/chemistry/*metabolism ; Cation Transport Proteins/metabolism ; Copper/chemistry/*metabolism ; Crystallography, X-Ray ; Ligands ; Metallochaperones/*antagonists & inhibitors/chemistry/*metabolism ; Models, Chemical ; Models, Molecular ; Molecular Structure ; Molybdenum/chemistry/*metabolism/*pharmacology ; Oxidation-Reduction ; Physicochemical Processes ; Protein Conformation ; Saccharomyces cerevisiae Proteins/*antagonists & inhibitors/chemistry/*metabolism
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  • 50
    Publication Date: 2009-08-08
    Description: Pathogens can use DNA recombination to promote antigenic variation (Av) of surface structures to avoid immune detection. We identified a cis-acting DNA sequence near the antigenically variable pilin locus of the human pathogen, Neisseria gonorrhoeae. This 16-base pair guanine (G)-rich sequence was required for pilin Av and formed a guanine quartet (G4) structure in vitro. Individual mutations that disrupted the structure also blocked pilin Av and prevented nicks required for recombination from occurring within the G4 region. A compound that binds and stabilizes G4 structures also inhibited pilin Av and prevented nicks from occurring on the G-rich strand. This site constitutes a recombination initiation sequence/structure that directs gene conversion to a specific chromosomal locus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803317/" 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/PMC2803317/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cahoon, Laty A -- Seifert, H Steven -- R01 AI044239/AI/NIAID NIH HHS/ -- R01 AI044239-08/AI/NIAID NIH HHS/ -- R01 AI044239-09/AI/NIAID NIH HHS/ -- R01 AI044239-10/AI/NIAID NIH HHS/ -- R01 AI055977/AI/NIAID NIH HHS/ -- R01 AI055977-03/AI/NIAID NIH HHS/ -- R01 AI055977-04/AI/NIAID NIH HHS/ -- R01 AI055977-05/AI/NIAID NIH HHS/ -- R01AI044239/AI/NIAID NIH HHS/ -- R01AI055977/AI/NIAID NIH HHS/ -- R37 AI033493/AI/NIAID NIH HHS/ -- R37 AI033493-14/AI/NIAID NIH HHS/ -- R37 AI033493-15/AI/NIAID NIH HHS/ -- R37 AI033493-16/AI/NIAID NIH HHS/ -- R37AI033493/AI/NIAID NIH HHS/ -- T32GM08061/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):764-7. doi: 10.1126/science.1175653.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661435" target="_blank"〉PubMed〈/a〉
    Keywords: *Antigenic Variation ; Base Pairing ; Base Sequence ; DNA Damage ; DNA, Bacterial/chemistry/*genetics ; Fimbriae Proteins/chemistry/*genetics/*immunology ; Fimbriae, Bacterial ; Gene Conversion ; Guanine/chemistry ; Mesoporphyrins/metabolism/pharmacology ; Neisseria gonorrhoeae/*genetics/growth & development/*immunology ; Oligodeoxyribonucleotides/chemistry ; Recombination, Genetic
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  • 51
    Publication Date: 2009-02-14
    Description: Infection by human rhinovirus (HRV) is a major cause of upper and lower respiratory tract disease worldwide and displays considerable phenotypic variation. We examined diversity by completing the genome sequences for all known serotypes (n = 99). Superimposition of capsid crystal structure and optimal-energy RNA configurations established alignments and phylogeny. These revealed conserved motifs; clade-specific diversity, including a potential newly identified species (HRV-D); mutations in field isolates; and recombination. In analogy with poliovirus, a hypervariable 5' untranslated region tract may affect virulence. A configuration consistent with nonscanning internal ribosome entry was found in all HRVs and may account for rapid translation. The data density from complete sequences of the reference HRVs provided high resolution for this degree of modeling and serves as a platform for full genome-based epidemiologic studies and antiviral or vaccine development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923423/" 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/PMC3923423/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Palmenberg, Ann C -- Spiro, David -- Kuzmickas, Ryan -- Wang, Shiliang -- Djikeng, Appolinaire -- Rathe, Jennifer A -- Fraser-Liggett, Claire M -- Liggett, Stephen B -- R01 HL091490/HL/NHLBI NIH HHS/ -- U19 AI070503/AI/NIAID NIH HHS/ -- U19-AI070503/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):55-9. doi: 10.1126/science.1165557. Epub 2009 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular Virology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213880" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; 5' Untranslated Regions ; Base Composition ; Base Sequence ; Codon, Terminator ; *Evolution, Molecular ; *Genome, Viral ; Humans ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Open Reading Frames ; Phylogeny ; Picornaviridae Infections/virology ; Polyproteins/biosynthesis/chemistry/genetics ; RNA, Viral/chemistry/*genetics ; Recombination, Genetic ; Respiratory Tract Infections/virology ; Rhinovirus/classification/*genetics/ultrastructure ; Sequence Alignment ; Sequence Analysis, RNA ; Serotyping ; Viral Proteins/biosynthesis/chemistry/genetics
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  • 52
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):664. doi: 10.1126/science.325_664.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661393" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Patents as Topic ; *Phylogeny ; *Sequence Analysis, DNA ; United States
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  • 53
    Publication Date: 2009-03-03
    Description: Influenza virus presents an important and persistent threat to public health worldwide, and current vaccines provide immunity to viral isolates similar to the vaccine strain. High-affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Cocrystal structures were determined at 2.2 and 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1 and HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758658/" 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/PMC2758658/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ekiert, Damian C -- Bhabha, Gira -- Elsliger, Marc-Andre -- Friesen, Robert H E -- Jongeneelen, Mandy -- Throsby, Mark -- Goudsmit, Jaap -- Wilson, Ian A -- AI-058113/AI/NIAID NIH HHS/ -- P01 AI058113/AI/NIAID NIH HHS/ -- P01 AI058113-040002/AI/NIAID NIH HHS/ -- U54 GM074898/GM/NIGMS NIH HHS/ -- U54 GM074898-03/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):246-51. doi: 10.1126/science.1171491. Epub 2009 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, 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/19251591" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Viral/chemistry/*immunology ; *Antibody Affinity ; Antigens, Viral/chemistry/*immunology ; *Binding Sites, Antibody ; Crystallization ; Crystallography, X-Ray ; Epitopes/immunology ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/*immunology ; Humans ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Hydrophobic and Hydrophilic Interactions ; Immunoglobulin Fab Fragments/chemistry/*immunology ; Influenza A Virus, H1N1 Subtype/*immunology ; Influenza A Virus, H5N1 Subtype/*immunology ; Influenza Vaccines ; Membrane Fusion ; Models, Molecular ; Neutralization Tests ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sherman, William -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):46-7. doi: 10.1126/science.1172136.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Functional Nanomaterials, Brookhaven National Laboratory, Upton, NY 11973, USA. wsherman@bnl.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342576" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA/chemistry ; Furocoumarins/chemistry ; Hot Temperature ; Nanotechnology/*methods ; Nucleic Acid Conformation ; Nucleic Acid Denaturation ; Nucleic Acid Hybridization ; Ultraviolet Rays
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1337-9. doi: 10.1126/science.326.5958.1337.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965731" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid beta-Peptides/chemistry/metabolism ; Animals ; Humans ; Nerve Tissue Proteins/chemistry/metabolism ; Neurodegenerative Diseases/*etiology/metabolism/therapy ; Neurons/chemistry/metabolism ; Nuclear Proteins/chemistry/metabolism ; *Prion Diseases ; Prions/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Proteins/*chemistry/metabolism ; alpha-Synuclein/chemistry/metabolism ; tau Proteins/chemistry
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  • 56
    Publication Date: 2009-09-12
    Description: Activation of Rho guanosine triphosphatases (GTPases) to the guanine triphosphate (GTP)-bound state is a critical event in their regulation of the cytoskeleton and cell signaling. Members of the DOCK family of guanine nucleotide exchange factors (GEFs) are important activators of Rho GTPases, but the mechanism of activation by their catalytic DHR2 domain is unknown. Through structural analysis of DOCK9-Cdc42 complexes, we identify a nucleotide sensor within the alpha10 helix of the DHR2 domain that contributes to release of guanine diphosphate (GDP) and then to discharge of the activated GTP-bound Cdc42. Magnesium exclusion, a critical factor in promoting GDP release, is mediated by a conserved valine residue within this sensor, whereas binding of GTP-Mg2+ to the nucleotide-free complex results in magnesium-inducing displacement of the sensor to stimulate discharge of Cdc42-GTP. These studies identify an unusual mechanism of GDP release and define the complete GEF catalytic cycle from GDP dissociation followed by GTP binding and discharge of the activated GTPase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Jing -- Zhang, Ziguo -- Roe, S Mark -- Marshall, Christopher J -- Barford, David -- 10433/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1398-402. doi: 10.1126/science.1174468.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745154" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Enzyme Activation ; Guanine Nucleotide Exchange Factors/*chemistry/*metabolism ; Guanosine Diphosphate/*metabolism ; Guanosine Triphosphate/*metabolism ; Humans ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; cdc42 GTP-Binding Protein/*chemistry/*metabolism
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  • 57
    Publication Date: 2009-11-26
    Description: The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. Although Sec complexes can form oligomers, it has been suggested that a single copy may serve as an active PCC. We determined subnanometer-resolution cryo-electron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination with biochemical data, we found that in both idle and active states, the Sec complex is not oligomeric and interacts mainly via two cytoplasmic loops with the universal ribosomal adaptor site. In the active state, the ribosomal tunnel and a central pore of the monomeric PCC were occupied by the nascent chain, contacting loop 6 of the Sec complex. This provides a structural basis for the activity of a solitary Sec complex in cotranslational protein translocation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920595/" 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/PMC2920595/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becker, Thomas -- Bhushan, Shashi -- Jarasch, Alexander -- Armache, Jean-Paul -- Funes, Soledad -- Jossinet, Fabrice -- Gumbart, James -- Mielke, Thorsten -- Berninghausen, Otto -- Schulten, Klaus -- Westhof, Eric -- Gilmore, Reid -- Mandon, Elisabet C -- Beckmann, Roland -- GM35687/GM/NIGMS NIH HHS/ -- P41 RR005969/RR/NCRR NIH HHS/ -- P41 RR005969-19/RR/NCRR NIH HHS/ -- P41-RR05969/RR/NCRR NIH HHS/ -- R01-GM067887/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1369-73. doi: 10.1126/science.1178535. Epub 2009 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Center Munich and Center for Integrated Protein Science, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universitat Munchen, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933108" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cryoelectron Microscopy ; Dogs ; Image Processing, Computer-Assisted ; Membrane Proteins/*chemistry/*metabolism/ultrastructure ; Models, Molecular ; *Protein Biosynthesis ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; *Protein Transport ; Proteins/chemistry/*metabolism/ultrastructure ; Ribosomes/*metabolism/ultrastructure ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism/ultrastructure
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  • 58
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feuillet, Catherine -- Eversole, Kellye -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1071-2. doi: 10.1126/science.1183463.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UMR INRA-UBP, Genetique, Diversite et Ecophysiologie des Cereales, 63100 Clermont-Ferrand, France. catherine.feuillet@clermont.inra.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965417" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chromosome Mapping ; Crops, Agricultural/genetics ; Genes, Plant ; Genetic Variation ; *Genome, Plant ; Haplotypes ; Hybrid Vigor ; Hybridization, Genetic ; *Sequence Analysis, DNA ; Zea mays/*genetics/physiology
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  • 59
    Publication Date: 2009-12-08
    Description: The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862588/" 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/PMC2862588/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Kwon, Young Do -- Zhou, Tongqing -- Wu, Xueling -- O'Dell, Sijy -- Cavacini, Lisa -- Hessell, Ann J -- Pancera, Marie -- Tang, Min -- Xu, Ling -- Yang, Zhi-Yong -- Zhang, Mei-Yun -- Arthos, James -- Burton, Dennis R -- Dimitrov, Dimiter S -- Nabel, Gary J -- Posner, Marshall R -- Sodroski, Joseph -- Wyatt, Richard -- Mascola, John R -- Kwong, Peter D -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1123-7. doi: 10.1126/science.1175868.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965434" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Neutralizing/chemistry/*immunology/metabolism ; Antigens, CD4/chemistry/*metabolism ; Binding Sites ; Binding Sites, Antibody ; Crystallography, X-Ray ; Epitopes ; HIV Antibodies/*chemistry/*immunology/metabolism ; HIV Envelope Protein gp120/*chemistry/*immunology/metabolism ; Hiv-1 ; Humans ; Hydrophobic and Hydrophilic Interactions ; *Immune Evasion ; Models, Molecular ; Molecular Sequence Data ; Peptide Fragments/chemistry/immunology/metabolism ; Protein Conformation
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  • 60
    Publication Date: 2009-04-25
    Description: The script of the ancient Indus civilization remains undeciphered. The hypothesis that the script encodes language has recently been questioned. Here, we present evidence for the linguistic hypothesis by showing that the script's conditional entropy is closer to those of natural languages than various types of nonlinguistic systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rao, Rajesh P N -- Yadav, Nisha -- Vahia, Mayank N -- Joglekar, Hrishikesh -- Adhikari, R -- Mahadevan, Iravatham -- New York, N.Y. -- Science. 2009 May 29;324(5931):1165. doi: 10.1126/science.1170391. Epub 2009 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA. rao@cs.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19389998" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Chromosomes, Human, Pair 2/genetics ; Escherichia coli Proteins/chemistry ; History, Ancient ; Humans ; India ; Language ; Linguistics/*history ; Pakistan ; Programming Languages ; Writing/*history
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  • 61
    Publication Date: 2009-11-11
    Description: Genetic changes contributing to phenotypic differences within or between species have been identified for a handful of traits, but the relationship between alleles underlying intraspecific polymorphism and interspecific divergence is largely unknown. We found that noncoding changes in the tan gene, as well as changes linked to the ebony gene, contribute to pigmentation divergence between closely related Drosophila species. Moreover, we found that alleles linked to tan and ebony fixed in one Drosophila species also contribute to variation within another species, and that multiple genotypes underlie similar phenotypes even within the same population. These alleles appear to predate speciation, which suggests that standing genetic variation present in the common ancestor gave rise to both intraspecific polymorphism and interspecific divergence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wittkopp, Patricia J -- Stewart, Emma E -- Arnold, Lisa L -- Neidert, Adam H -- Haerum, Belinda K -- Thompson, Elizabeth M -- Akhras, Saleh -- Smith-Winberry, Gabriel -- Shefner, Laura -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):540-4. doi: 10.1126/science.1176980.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA. wittkopp@umich.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19900891" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Animals, Genetically Modified ; Base Sequence ; Chromosomal Proteins, Non-Histone/*genetics/metabolism ; Crosses, Genetic ; DNA-Binding Proteins/*genetics/metabolism ; Drosophila/classification/*genetics/growth & development/metabolism ; Drosophila Proteins/*genetics/metabolism ; Female ; Gene Expression ; Gene Expression Regulation ; Genes, Insect ; Genetic Speciation ; Genotype ; Introns ; Male ; Molecular Sequence Data ; Phenotype ; Pigmentation/*genetics ; *Polymorphism, Genetic ; Quantitative Trait Loci ; Species Specificity
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steitz, Thomas A -- New York, N.Y. -- Science. 2009 Feb 27;323(5918):1181. doi: 10.1126/science.1171157.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA. thomas.steitz@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19251620" target="_blank"〉PubMed〈/a〉
    Keywords: Biochemistry/*history ; Biophysics/*history ; History, 20th Century ; History, 21st Century ; Protein Conformation ; Proteins/*chemistry/metabolism ; Ribonuclease, Pancreatic/chemistry/metabolism ; United States
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  • 63
    Publication Date: 2009-04-25
    Description: CRM1 mediates nuclear export of numerous unrelated cargoes, which may carry a short leucine-rich nuclear export signal or export signatures that include folded domains. How CRM1 recognizes such a variety of cargoes has been unknown up to this point. Here we present the crystal structure of the SPN1.CRM1.RanGTP export complex at 2.5 angstrom resolution (where SPN1 is snurportin1 and RanGTP is guanosine 5' triphosphate-bound Ran). SPN1 is a nuclear import adapter for cytoplasmically assembled, m(3)G-capped spliceosomal U snRNPs (small nuclear ribonucleoproteins). The structure shows how CRM1 can specifically return the cargo-free form of SPN1 to the cytoplasm. The extensive contact area includes five hydrophobic residues at the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as well as numerous hydrophilic contacts of CRM1 to m(3)G cap-binding domain and carboxyl-terminal residues of SPN1. The structure suggests that RanGTP promotes cargo-binding to CRM1 solely through long-range conformational changes in the exportin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monecke, Thomas -- Guttler, Thomas -- Neumann, Piotr -- Dickmanns, Achim -- Gorlich, Dirk -- Ficner, Ralf -- New York, N.Y. -- Science. 2009 May 22;324(5930):1087-91. doi: 10.1126/science.1173388. Epub 2009 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abteilung fur Molekulare Strukturbiologie, Institut fur Mikrobiologie und Genetik, GZMB, Georg-August-Universitat Gottingen, Justus-von-Liebig-Weg 11, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19389996" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Crystallography, X-Ray ; Guanosine Triphosphate/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Karyopherins/*chemistry/metabolism ; Mice ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA Cap-Binding Proteins/*chemistry/metabolism ; Receptors, Cytoplasmic and Nuclear/*chemistry/metabolism ; beta Karyopherins/metabolism ; ran GTP-Binding Protein/*chemistry/metabolism
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Guanyang -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1672; author reply 1672. doi: 10.1126/science.323.5922.1672.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325099" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Biodiversity ; *Biological Specimen Banks ; Databases, Factual ; *Databases, Nucleic Acid ; National Library of Medicine (U.S.) ; *Natural History ; United States
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  • 65
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-01-31
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742222/" 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/PMC2742222/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Best, Robert B -- Hummer, Gerhard -- Z01 DK029033-08/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):593-4. doi: 10.1126/science.1169555.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179519" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/*metabolism ; Calmodulin/*chemistry/*metabolism ; Humans ; Ligands ; Microscopy, Atomic Force ; Myosin-Light-Chain Kinase/chemistry/*metabolism ; Peptide Fragments/metabolism ; Protein Binding ; Protein Conformation ; Protein Folding
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  • 66
    Publication Date: 2009-01-31
    Description: Single-molecule force spectroscopy allows superb mechanical control of protein conformation. We used a custom-built low-drift atomic force microscope to observe mechanically induced conformational equilibrium fluctuations of single molecules of the eukaryotic calcium-dependent signal transducer calmodulin (CaM). From this data, the ligand dependence of the full energy landscape can be reconstructed. We find that calcium ions affect the folding kinetics of the individual CaM domains, whereas target peptides stabilize the already folded structure. Single-molecule data of full length CaM reveal that a wasp venom peptide binds noncooperatively to CaM with 2:1 stoichiometry, whereas a target enzyme peptide binds cooperatively with 1:1 stoichiometry. If mechanical load is applied directly to the target peptide, real-time binding/unbinding transitions can be observed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Junker, Jan Philipp -- Ziegler, Fabian -- Rief, Matthias -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):633-7. doi: 10.1126/science.1166191.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physik Department E22, Technische Universitat Munchen, James-Franck-Strasse, 85748 Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179531" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/*metabolism ; Calmodulin/*chemistry/*metabolism ; Humans ; Kinetics ; Ligands ; Microscopy, Atomic Force ; Monte Carlo Method ; Myosin-Light-Chain Kinase/chemistry/*metabolism ; Peptide Fragments/chemistry/metabolism ; Peptides/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Thermodynamics ; Wasp Venoms/chemistry/*metabolism
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monroe, Don -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):142-3. doi: 10.1126/science.325_142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19589978" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Conserved Sequence ; DNA/*genetics/metabolism ; DNA, Intergenic/genetics ; DNA-Binding Proteins/metabolism ; Evolution, Molecular ; Genes, Essential ; *Genome, Human ; Humans ; Mice ; Mutation ; RNA/genetics ; Regulatory Sequences, Nucleic Acid
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  • 68
    Publication Date: 2009-08-22
    Description: Protein biosynthesis on the ribosome requires repeated cycles of ratcheting, which couples rotation of the two ribosomal subunits with respect to each other, and swiveling of the head domain of the small subunit. However, the molecular basis for how the two ribosomal subunits rearrange contacts with each other during ratcheting while remaining stably associated is not known. Here, we describe x-ray crystal structures of the intact Escherichia coli ribosome, either in the apo-form (3.5 angstrom resolution) or with one (4.0 angstrom resolution) or two (4.0 angstrom resolution) anticodon stem-loop tRNA mimics bound, that reveal intermediate states of intersubunit rotation. In the structures, the interface between the small and large ribosomal subunits rearranges in discrete steps along the ratcheting pathway. Positioning of the head domain of the small subunit is controlled by interactions with the large subunit and with the tRNA bound in the peptidyl-tRNA site. The intermediates observed here provide insight into how tRNAs move into the hybrid state of binding that precedes the final steps of mRNA and tRNA translocation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919209/" 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/PMC2919209/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Wen -- Dunkle, Jack A -- Cate, Jamie H D -- CA92584/CA/NCI NIH HHS/ -- GM65050/GM/NIGMS NIH HHS/ -- R01 GM065050/GM/NIGMS NIH HHS/ -- R01 GM065050-08/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):1014-7. doi: 10.1126/science.1175275.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19696352" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon/chemistry/metabolism ; Crystallography, X-Ray ; Escherichia coli/chemistry/metabolism/*ultrastructure ; Escherichia coli Proteins/biosynthesis/chemistry/metabolism ; Nucleic Acid Conformation ; *Protein Biosynthesis ; Protein Conformation ; RNA, Bacterial/chemistry/metabolism ; RNA, Messenger/chemistry/metabolism ; RNA, Transfer, Met/chemistry/metabolism ; RNA, Transfer, Phe/chemistry/metabolism ; Ribosomal Proteins/chemistry/metabolism ; Ribosome Subunits, Large, Bacterial/chemistry/metabolism/ultrastructure ; Ribosome Subunits, Small, Bacterial/chemistry/metabolism/ultrastructure ; Ribosomes/chemistry/*metabolism/*ultrastructure
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  • 69
    Publication Date: 2009-06-06
    Description: Von Willebrand factor (VWF) is secreted as ultralarge multimers that are cleaved in the A2 domain by the metalloprotease ADAMTS13 to give smaller multimers. Cleaved VWF is activated by hydrodynamic forces found in arteriolar bleeding to promote hemostasis, whereas uncleaved VWF is activated at lower, physiologic shear stresses and causes thrombosis. Single-molecule experiments demonstrate that elongational forces in the range experienced by VWF in the vasculature unfold the A2 domain, and only the unfolded A2 domain is cleaved by ADAMTS13. In shear flow, tensile force on a VWF multimer increases with the square of multimer length and is highest at the middle, providing an efficient mechanism for homeostatic regulation of VWF size distribution by force-induced A2 unfolding and cleavage by ADAMTS13, as well as providing a counterbalance for VWF-mediated platelet aggregation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753189/" 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/PMC2753189/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Xiaohui -- Halvorsen, Kenneth -- Zhang, Cheng-Zhong -- Wong, Wesley P -- Springer, Timothy A -- HL-48675/HL/NHLBI NIH HHS/ -- P01 HL048675/HL/NHLBI NIH HHS/ -- P01 HL048675-16/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 5;324(5932):1330-4. doi: 10.1126/science.1170905.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19498171" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins/*metabolism ; Binding Sites ; Blood Coagulation/physiology ; *Hemostasis ; Humans ; Kinetics ; *Mechanical Phenomena ; Optical Tweezers ; Platelet Aggregation ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Tertiary ; Stress, Mechanical ; Thermodynamics ; von Willebrand Factor/*chemistry/*metabolism
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  • 70
    Publication Date: 2009-09-05
    Description: Coated vesicles concentrate and package cargo molecules to mediate their efficient transport between intracellular compartments. Cytosolic coat proteins such as clathrin and adaptor complexes and coat protein complex I (COPI) and COPII self-assemble to deform the membrane and interact directly with cargo molecules to capture them in nascent buds. The guanosine triphosphatases (GTPases) Arf, Sar1, and dynamin are core components of the coated vesicle machinery. These GTPases, which associate with and dissociate from donor membranes in a guanosine triphosphate-dependent manner, can also actively remodel membranes. Recent evidence suggests that, although structurally diverse, Arf family GTPases and dynamin may play mechanistically similar roles as fidelity monitors that govern cargo packaging and coated vesicle maturation and as components of the fission machinery to mediate vesicle release.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864031/" 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/PMC2864031/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pucadyil, Thomas J -- Schmid, Sandra L -- GM42455/GM/NIGMS NIH HHS/ -- GM73165/GM/NIGMS NIH HHS/ -- MH61345/MH/NIMH NIH HHS/ -- R01 GM042455/GM/NIGMS NIH HHS/ -- R01 GM042455-20/GM/NIGMS NIH HHS/ -- R01 GM073165/GM/NIGMS NIH HHS/ -- R01 GM073165-04/GM/NIGMS NIH HHS/ -- R37 MH061345/MH/NIMH NIH HHS/ -- R37 MH061345-10/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1217-20. doi: 10.1126/science.1171004.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, The Scripps Research Institute (TSRI), 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/19729648" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factor 1/chemistry/metabolism ; Animals ; COP-Coated Vesicles/chemistry/*metabolism/ultrastructure ; Cell Membrane/*metabolism/ultrastructure ; Clathrin-Coated Vesicles/chemistry/*metabolism/ultrastructure ; Dynamins/chemistry/metabolism ; GTP Phosphohydrolases/*metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Monomeric GTP-Binding Proteins/chemistry/metabolism ; Protein Conformation ; Vesicular Transport Proteins/metabolism
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  • 71
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-12-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1338. doi: 10.1126/science.326.5958.1338.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965732" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion ; Endocrine Cells/chemistry/metabolism ; Humans ; Melanins/biosynthesis ; Nervous System Physiological Phenomena ; Prions/*chemistry ; Protein Conformation ; *Protein Folding ; Proteins/*chemistry/physiology ; Secretory Vesicles/chemistry/metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 72
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-11-26
    Description: TAL effectors of plant pathogenic bacteria in the genus Xanthomonas bind host DNA and activate genes that contribute to disease or turn on defense. Target specificity depends on an effector-variable number of typically 34 amino acid repeats, but the mechanism of recognition is not understood. We show that a repeat-variable pair of residues specifies the nucleotides in the target site, one pair to one nucleotide, with no apparent context dependence. Our finding represents a previously unknown mechanism for protein-DNA recognition that explains TAL effector specificity, enables target site prediction, and opens prospects for use of TAL effectors in research and biotechnology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moscou, Matthew J -- Bogdanove, Adam J -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1501. doi: 10.1126/science.1178817. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology and Bioinformatics and Computational Biology Program, Iowa State University, Ames, IA 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933106" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry/metabolism ; Base Sequence ; Computational Biology ; DNA, Plant/chemistry/genetics/*metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Molecular Sequence Data ; Nucleotides/metabolism ; Oryza/*genetics/microbiology ; Promoter Regions, Genetic ; Protein Array Analysis ; Repetitive Sequences, Amino Acid ; *Transcriptional Activation ; Xanthomonas/*metabolism/pathogenicity
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  • 73
    Publication Date: 2009-01-20
    Description: Retroviruses have the potential to acquire host cell-derived genetic material during reverse transcription and can integrate into the genomes of larger, more complex DNA viruses. In contrast, RNA viruses were believed not to integrate into the host's genome under any circumstances. We found that illegitimate recombination between an exogenous nonretroviral RNA virus, lymphocytic choriomeningitis virus, and the endogenous intracisternal A-type particle (IAP) retrotransposon occurred and led to reverse transcription of exogenous viral RNA. The resulting complementary DNA was integrated into the host's genome with an IAP element. Thus, RNA viruses should be closely scrutinized for any capacity to interact with endogenous retroviral elements before their approval for therapeutic use in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geuking, Markus B -- Weber, Jacqueline -- Dewannieux, Marie -- Gorelik, Elieser -- Heidmann, Thierry -- Hengartner, Hans -- Zinkernagel, Rolf M -- Hangartner, Lars -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):393-6. doi: 10.1126/science.1167375.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland. geuking@mcmaster.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arenaviridae Infections/virology ; Base Sequence ; Cell Line ; DNA, Complementary/*genetics ; Genes, Intracisternal A-Particle/*genetics ; Glycoproteins/genetics ; Humans ; Lymphocytic choriomeningitis virus/*genetics ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Polymerase Chain Reaction ; RNA, Viral/*genetics ; *Recombination, Genetic ; *Reverse Transcription ; Transfection ; Viral Proteins/genetics ; *Virus Integration
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  • 74
    Publication Date: 2009-10-10
    Description: We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858594/" 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/PMC2858594/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lieberman-Aiden, Erez -- van Berkum, Nynke L -- Williams, Louise -- Imakaev, Maxim -- Ragoczy, Tobias -- Telling, Agnes -- Amit, Ido -- Lajoie, Bryan R -- Sabo, Peter J -- Dorschner, Michael O -- Sandstrom, Richard -- Bernstein, Bradley -- Bender, M A -- Groudine, Mark -- Gnirke, Andreas -- Stamatoyannopoulos, John -- Mirny, Leonid A -- Lander, Eric S -- Dekker, Job -- HG003143/HG/NHGRI NIH HHS/ -- R01 HG003143/HG/NHGRI NIH HHS/ -- R01 HG003143-06/HG/NHGRI NIH HHS/ -- R01HL06544/HL/NHLBI NIH HHS/ -- R37DK44746/DK/NIDDK NIH HHS/ -- T32 HG002295/HG/NHGRI NIH HHS/ -- U54HG004592/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):289-93. doi: 10.1126/science.1181369.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815776" target="_blank"〉PubMed〈/a〉
    Keywords: Biotin ; Cell Line, Transformed ; Cell Nucleus/*ultrastructure ; Chromatin/*chemistry ; Chromatin Immunoprecipitation ; *Chromosomes, Human/chemistry/ultrastructure ; Computational Biology ; DNA/*chemistry ; Gene Library ; *Genome, Human ; Humans ; In Situ Hybridization, Fluorescence ; Models, Molecular ; Monte Carlo Method ; Nucleic Acid Conformation ; Principal Component Analysis ; Protein Conformation ; Sequence Analysis, DNA
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  • 75
    Publication Date: 2009-05-30
    Description: Adenosine-to-inosine (A-to-I) RNA editing leads to transcriptome diversity and is important for normal brain function. To date, only a handful of functional sites have been identified in mammals. We developed an unbiased assay to screen more than 36,000 computationally predicted nonrepetitive A-to-I sites using massively parallel target capture and DNA sequencing. A comprehensive set of several hundred human RNA editing sites was detected by comparing genomic DNA with RNAs from seven tissues of a single individual. Specificity of our profiling was supported by observations of enrichment with known features of targets of adenosine deaminases acting on RNA (ADAR) and validation by means of capillary sequencing. This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing-related human diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Jin Billy -- Levanon, Erez Y -- Yoon, Jung-Ki -- Aach, John -- Xie, Bin -- Leproust, Emily -- Zhang, Kun -- Gao, Yuan -- Church, George M -- New York, N.Y. -- Science. 2009 May 29;324(5931):1210-3. doi: 10.1126/science.1170995.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478186" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/metabolism ; Adrenal Glands/metabolism ; Alu Elements ; Animals ; Base Sequence ; Brain/*metabolism ; DNA/*genetics ; DNA, Complementary ; *Genome, Human ; Humans ; Intestine, Small/metabolism ; Mice ; *RNA Editing ; RNA, Double-Stranded/chemistry/genetics/metabolism ; RNA, Messenger/chemistry/genetics/*metabolism ; RNA-Binding Proteins ; Sequence Analysis, DNA
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  • 76
    Publication Date: 2009-12-08
    Description: Rates and mechanisms of intron gain and loss have traditionally been inferred from alignments of highly conserved genes sampled from phylogenetically distant taxa. We report a population-genomic approach that detected 24 discordant intron/exon boundaries between the whole-genome sequences of two Daphnia pulex isolates. Sequencing of presence/absence loci across a collection of D. pulex isolates and outgroup Daphnia species shows that most polymorphisms are a consequence of recent gains, with parallel gains often occurring at the same locations in independent allelic lineages. More than half of the recent gains are associated with short sequence repeats, suggesting an origin via repair of staggered double-strand breaks. By comparing the allele-frequency spectrum of intron-gain alleles with that for derived single-base substitutions, we also provide evidence that newly arisen introns are intrinsically deleterious and tend to accumulate in population-genetic settings where random genetic drift is a relatively strong force.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878872/" 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/PMC3878872/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Wenli -- Tucker, Abraham E -- Sung, Way -- Thomas, W Kelley -- Lynch, Michael -- R01 GM036827/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1260-2. doi: 10.1126/science.1179302.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Indiana University, Bloomington, IN 47405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965475" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Computational Biology ; DNA Breaks, Double-Stranded ; DNA Repair ; Daphnia/*genetics ; Exons ; *Genome ; *Introns ; Molecular Sequence Data ; Phylogeny ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Repetitive Sequences, Nucleic Acid ; Time Factors
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  • 77
    Publication Date: 2009-01-10
    Description: Strict one-to-one correspondence between codons and amino acids is thought to be an essential feature of the genetic code. However, we report that one codon can code for two different amino acids with the choice of the inserted amino acid determined by a specific 3' untranslated region structure and location of the dual-function codon within the messenger RNA (mRNA). We found that the codon UGA specifies insertion of selenocysteine and cysteine in the ciliate Euplotes crassus, that the dual use of this codon can occur even within the same gene, and that the structural arrangements of Euplotes mRNA preserve location-dependent dual function of UGA when expressed in mammalian cells. Thus, the genetic code supports the use of one codon to code for multiple amino acids.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088105/" 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/PMC3088105/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turanov, Anton A -- Lobanov, Alexey V -- Fomenko, Dmitri E -- Morrison, Hilary G -- Sogin, Mitchell L -- Klobutcher, Lawrence A -- Hatfield, Dolph L -- Gladyshev, Vadim N -- AI058054/AI/NIAID NIH HHS/ -- GM061603/GM/NIGMS NIH HHS/ -- GM065204/GM/NIGMS NIH HHS/ -- R01 GM061603/GM/NIGMS NIH HHS/ -- R01 GM061603-04S2/GM/NIGMS NIH HHS/ -- ZIA BC010767-03/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):259-61. doi: 10.1126/science.1164748.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE 68588, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19131629" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Codon/*genetics ; Codon, Terminator/*genetics ; Cysteine/*genetics/metabolism ; Euplotes/chemistry/*genetics ; *Genetic Code ; Humans ; Molecular Sequence Data ; Mutation ; Protozoan Proteins/biosynthesis/chemistry/genetics ; RNA, Protozoan/genetics/metabolism ; RNA, Transfer, Amino Acid-Specific/chemistry/genetics ; RNA, Transfer, Cys/chemistry/genetics ; Recombinant Fusion Proteins/metabolism ; Selenocysteine/*genetics/metabolism ; Selenoproteins/biosynthesis/chemistry/*genetics
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  • 78
    Publication Date: 2009-08-08
    Description: Protein synthesis involves the accurate attachment of amino acids to their matching transfer RNA (tRNA) molecules. Mistranslating the amino acids serine or glycine for alanine is prevented by the function of independent but collaborative aminoacylation and editing domains of alanyl-tRNA synthetases (AlaRSs). We show that the C-Ala domain plays a key role in AlaRS function. The C-Ala domain is universally tethered to the editing domain both in AlaRS and in many homologous free-standing editing proteins. Crystal structure and functional analyses showed that C-Ala forms an ancient single-stranded nucleic acid binding motif that promotes cooperative binding of both aminoacylation and editing domains to tRNA(Ala). In addition, C-Ala may have played an essential role in the evolution of AlaRSs by coupling aminoacylation to editing to prevent mistranslation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559334/" 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/PMC4559334/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Min -- Chong, Yeeting E -- Beebe, Kirk -- Shapiro, Ryan -- Yang, Xiang-Lei -- Schimmel, Paul -- GM 15539/GM/NIGMS NIH HHS/ -- R01 GM015539/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):744-7. doi: 10.1126/science.1174343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, BCC-379, 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/19661429" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine-tRNA Ligase/*chemistry/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Bacteria/enzymology ; Base Sequence ; Crystallography, X-Ray ; Escherichia coli Proteins/chemistry/metabolism ; Evolution, Molecular ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Bacterial/chemistry/metabolism ; RNA, Transfer, Ala/*chemistry/*metabolism ; RNA, Transfer, Amino Acyl/chemistry/metabolism ; *Transfer RNA Aminoacylation
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  • 79
    Publication Date: 2009-03-21
    Description: The interface between antibody and antigen is often depicted as a lock and key, suggesting that an antibody surface can accommodate only one antigen. Here, we describe an antibody with an antigen binding site that binds two distinct proteins with high affinity. We isolated a variant of Herceptin, a therapeutic monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2), on the basis of its ability to simultaneously interact with vascular endothelial growth factor (VEGF). Crystallographic and mutagenesis studies revealed that distinct amino acids of this antibody, called bH1, engage HER2 and VEGF energetically, but there is extensive overlap between the antibody surface areas contacting the two antigens. An affinity-improved version of bH1 inhibits both HER2- and VEGF-mediated cell proliferation in vitro and tumor progression in mouse models. Such "two-in-one" antibodies challenge the monoclonal antibody paradigm of one binding site, one antigen. They could also provide new opportunities for antibody-based therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bostrom, Jenny -- Yu, Shang-Fan -- Kan, David -- Appleton, Brent A -- Lee, Chingwei V -- Billeci, Karen -- Man, Wenyan -- Peale, Franklin -- Ross, Sarajane -- Wiesmann, Christian -- Fuh, Germaine -- New York, N.Y. -- Science. 2009 Mar 20;323(5921):1610-4. doi: 10.1126/science.1165480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, 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/19299620" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Bispecific/chemistry/genetics/*immunology/therapeutic use ; Antibodies, Monoclonal/chemistry/genetics/*immunology/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibody Affinity ; Antibody Specificity ; Binding Sites, Antibody/genetics ; Cell Proliferation/drug effects ; Complementarity Determining Regions/genetics/immunology ; Crystallography, X-Ray ; Epitopes/immunology/metabolism ; Genetic Engineering ; Humans ; Mice ; Models, Molecular ; Mutagenesis ; Neoplasms, Experimental/drug therapy ; Protein Conformation ; Protein Structure, Tertiary ; Receptor, ErbB-2/chemistry/*immunology/metabolism ; Thermodynamics ; Trastuzumab ; Vascular Endothelial Growth Factor A/chemistry/*immunology/metabolism ; Xenograft Model Antitumor Assays
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  • 80
    Publication Date: 2009-09-19
    Description: Retroviruses can leave a "fossil record" in their hosts' genomes in the form of endogenous retroviruses. Foamy viruses, complex retroviruses that infect mammals, have been notably absent from this record. We have found an endogenous foamy virus within the genomes of sloths and show that foamy viruses were infecting mammals more than 100 million years ago and codiverged with their hosts across an entire geological era. Our analysis highlights the role of evolutionary constraint in maintaining viral genome structure and indicates that accessory genes and mammalian mechanisms of innate immunity are the products of macroevolutionary conflict played out over a geological time scale.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katzourakis, Aris -- Gifford, Robert J -- Tristem, Michael -- Gilbert, M Thomas P -- Pybus, Oliver G -- New York, N.Y. -- Science. 2009 Sep 18;325(5947):1512. doi: 10.1126/science.1174149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zoology Department, University of Oxford, Oxford OX1 3PS, UK. aris.katzourakis@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19762636" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Endogenous Retroviruses/classification/*genetics ; *Evolution, Molecular ; Genome ; Genome, Viral ; Immunity, Innate ; Molecular Sequence Data ; Phylogeny ; Retroviridae Infections/veterinary/virology ; Sloths/classification/*genetics/immunology/*virology ; Spumavirus/classification/*genetics ; Time
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  • 81
    Publication Date: 2009-03-07
    Description: Genome-wide association studies (GWASs) are regularly used to map genomic regions contributing to common human diseases, but they often do not identify the precise causative genes and sequence variants. To identify causative type 1 diabetes (T1D) variants, we resequenced exons and splice sites of 10 candidate genes in pools of DNA from 480 patients and 480 controls and tested their disease association in over 30,000 participants. We discovered four rare variants that lowered T1D risk independently of each other (odds ratio = 0.51 to 0.74; P = 1.3 x 10(-3) to 2.1 x 10(-16)) in IFIH1 (interferon induced with helicase C domain 1), a gene located in a region previously associated with T1D by GWASs. These variants are predicted to alter the expression and structure of IFIH1 [MDA5 (melanoma differentiation-associated protein 5)], a cytoplasmic helicase that mediates induction of interferon response to viral RNA. This finding firmly establishes the role of IFIH1 in T1D and demonstrates that resequencing studies can pinpoint disease-causing genes in genomic regions initially identified by GWASs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707798/" 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/PMC2707798/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nejentsev, Sergey -- Walker, Neil -- Riches, David -- Egholm, Michael -- Todd, John A -- 061858/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2009 Apr 17;324(5925):387-9. doi: 10.1126/science.1167728. Epub 2009 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK. sn262@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19264985" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Case-Control Studies ; Codon, Nonsense ; DEAD-box RNA Helicases/chemistry/*genetics/metabolism ; Diabetes Mellitus, Type 1/*genetics ; Gene Frequency ; *Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Linkage Disequilibrium ; Molecular Sequence Data ; *Polymorphism, Single Nucleotide ; RNA Splice Sites ; Risk ; Risk Factors ; Sequence Analysis, DNA
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  • 82
    Publication Date: 2009-08-22
    Description: Elongation factor P (EF-P) is an essential protein that stimulates the formation of the first peptide bond in protein synthesis. Here we report the crystal structure of EF-P bound to the Thermus thermophilus 70S ribosome along with the initiator transfer RNA N-formyl-methionyl-tRNA(i) (fMet-tRNA(i)(fMet)) and a short piece of messenger RNA (mRNA) at a resolution of 3.5 angstroms. EF-P binds to a site located between the binding site for the peptidyl tRNA (P site) and the exiting tRNA (E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA. Domain II of EF-P interacts with the ribosomal protein L1, which results in the largest movement of the L1 stalk that has been observed in the absence of ratcheting of the ribosomal subunits. EF-P facilitates the proper positioning of the fMet-tRNA(i)(fMet) for the formation of the first peptide bond during translation initiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296453/" 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/PMC3296453/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blaha, Gregor -- Stanley, Robin E -- Steitz, Thomas A -- GM22778/GM/NIGMS NIH HHS/ -- P01 GM022778/GM/NIGMS NIH HHS/ -- P01 GM022778-36/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):966-70. doi: 10.1126/science.1175800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19696344" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Models, Molecular ; *Peptide Chain Initiation, Translational ; Peptide Elongation Factors/*chemistry/*metabolism ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Bacterial/chemistry/metabolism ; RNA, Messenger/chemistry/metabolism ; RNA, Transfer, Met/chemistry/metabolism ; Ribosomal Proteins/metabolism ; Ribosome Subunits, Large, Bacterial/metabolism ; Ribosome Subunits, Small, Bacterial/metabolism ; Ribosomes/*metabolism ; Thermus thermophilus/chemistry/*metabolism
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  • 83
    Publication Date: 2009-10-10
    Description: Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lombardi, Vincent C -- Ruscetti, Francis W -- Das Gupta, Jaydip -- Pfost, Max A -- Hagen, Kathryn S -- Peterson, Daniel L -- Ruscetti, Sandra K -- Bagni, Rachel K -- Petrow-Sadowski, Cari -- Gold, Bert -- Dean, Michael -- Silverman, Robert H -- Mikovits, Judy A -- CA104943/CA/NCI NIH HHS/ -- HHSN26120080001E/PHS HHS/ -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):585-9. doi: 10.1126/science.1179052. Epub 2009 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whittemore Peterson Institute, Reno, NV 89557, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19815723" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/blood ; B-Lymphocytes/immunology/virology ; Base Sequence ; Cell Line ; Cell Line, Tumor ; Coculture Techniques ; DNA/genetics ; Fatigue Syndrome, Chronic/*virology ; Gammaretrovirus/genetics/immunology/*isolation & purification/physiology ; Gene Products, env/analysis ; Gene Products, gag/analysis ; Genome, Viral ; Humans ; Leukocytes, Mononuclear/*virology ; Lymphocyte Activation ; Male ; Mice ; Molecular Sequence Data ; Prostatic Neoplasms/virology ; Retroviridae Infections/epidemiology/transmission/*virology ; T-Lymphocytes/immunology/virology ; Tumor Virus Infections/epidemiology/transmission/*virology
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, Claire -- New York, N.Y. -- Science. 2009 Jul 31;325(5940):526. doi: 10.1126/science.325_526.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19644082" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA Primers ; DNA, Chloroplast/*genetics ; *Genes, Plant ; Genetic Markers ; Plants/*classification/*genetics
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  • 85
    Publication Date: 2009-11-26
    Description: The phytohormone abscisic acid (ABA) acts in seed dormancy, plant development, drought tolerance, and adaptive responses to environmental stresses. Structural mechanisms mediating ABA receptor recognition and signaling remain unknown but are essential for understanding and manipulating abiotic stress resistance. Here, we report structures of pyrabactin resistance 1 (PYR1), a prototypical PYR/PYR1-like (PYL)/regulatory component of ABA receptor (RCAR) protein that functions in early ABA signaling. The crystallographic structure reveals an alpha/beta helix-grip fold and homodimeric assembly, verified in vivo by coimmunoprecipitation. ABA binding within a large internal cavity switches structural motifs distinguishing ABA-free "open-lid" from ABA-bound "closed-lid" conformations. Small-angle x-ray scattering suggests that ABA signals by converting PYR1 to a more compact, symmetric closed-lid dimer. Site-directed PYR1 mutants designed to disrupt hormone binding lose ABA-triggered interactions with type 2C protein phosphatase partners in planta.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835493/" 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/PMC2835493/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishimura, Noriyuki -- Hitomi, Kenichi -- Arvai, Andrew S -- Rambo, Robert P -- Hitomi, Chiharu -- Cutler, Sean R -- Schroeder, Julian I -- Getzoff, Elizabeth D -- ES010337/ES/NIEHS NIH HHS/ -- GM060396/GM/NIGMS NIH HHS/ -- GM37684/GM/NIGMS NIH HHS/ -- P42 ES010337/ES/NIEHS NIH HHS/ -- P42 ES010337-10S20008/ES/NIEHS NIH HHS/ -- R01 GM060396/GM/NIGMS NIH HHS/ -- R01 GM060396-08/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Dec 4;326(5958):1373-9. doi: 10.1126/science.1181829. Epub 2009 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Sciences, Cell and Developmental Biology Section, University of California at San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933100" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Immunoprecipitation ; Membrane Transport Proteins/*chemistry/genetics/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutant Proteins/chemistry/metabolism ; Phosphoprotein Phosphatases/metabolism ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Subunits/chemistry/metabolism ; Scattering, Small Angle ; *Signal Transduction ; X-Ray Diffraction
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  • 86
    Publication Date: 2009-09-12
    Description: Methylation of ribosomal RNA (rRNA) is required for optimal protein synthesis. Multiple 2'-O-ribose methylations are carried out by box C/D guide ribonucleoproteins [small ribonucleoproteins (sRNPs) and small nucleolar ribonucleoproteins (snoRNPs)], which are conserved from archaea to eukaryotes. Methylation is dictated by base pairing between the specific guide RNA component of the sRNP or snoRNP and the target rRNA. We determined the structure of a reconstituted and catalytically active box C/D sRNP from the archaeon Methanocaldococcus jannaschii by single-particle electron microscopy. We found that archaeal box C/D sRNPs unexpectedly formed a dimeric structure with an alternative organization of their RNA and protein components that challenges the conventional view of their architecture. Mutational analysis demonstrated that this di-sRNP structure was relevant for the enzymatic function of archaeal box C/D sRNPs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975540/" 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/PMC2975540/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bleichert, Franziska -- Gagnon, Keith T -- Brown, Bernard A 2nd -- Maxwell, E Stuart -- Leschziner, Andres E -- Unger, Vinzenz M -- Baserga, Susan J -- R01 GM052581/GM/NIGMS NIH HHS/ -- R01 GM052581-15/GM/NIGMS NIH HHS/ -- R01GM52581/GM/NIGMS NIH HHS/ -- R01GM69699/GM/NIGMS NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 11;325(5946):1384-7. doi: 10.1126/science.1176099.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19745151" target="_blank"〉PubMed〈/a〉
    Keywords: Archaeal Proteins/*chemistry/metabolism/ultrastructure ; Base Sequence ; Chromosomal Proteins, Non-Histone/*chemistry ; Methanococcales/*chemistry ; Microscopy, Electron ; Models, Molecular ; Molecular Weight ; Nucleic Acid Conformation ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; RNA, Archaeal/*chemistry/ultrastructure ; Ribonucleoproteins/*chemistry/metabolism/ultrastructure
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  • 87
    Publication Date: 2009-11-26
    Description: The pathogenicity of many bacteria depends on the injection of effector proteins via type III secretion into eukaryotic cells in order to manipulate cellular processes. TAL (transcription activator-like) effectors from plant pathogenic Xanthomonas are important virulence factors that act as transcriptional activators in the plant cell nucleus, where they directly bind to DNA via a central domain of tandem repeats. Here, we show how target DNA specificity of TAL effectors is encoded. Two hypervariable amino acid residues in each repeat recognize one base pair in the target DNA. Recognition sequences of TAL effectors were predicted and experimentally confirmed. The modular protein architecture enabled the construction of artificial effectors with new specificities. Our study describes the functionality of a distinct type of DNA binding domain and allows the design of DNA binding domains for biotechnology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boch, Jens -- Scholze, Heidi -- Schornack, Sebastian -- Landgraf, Angelika -- Hahn, Simone -- Kay, Sabine -- Lahaye, Thomas -- Nickstadt, Anja -- Bonas, Ulla -- New York, N.Y. -- Science. 2009 Dec 11;326(5959):1509-12. doi: 10.1126/science.1178811. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Institute of Biology, Martin-Luther-University Halle-Wittenberg, Weinbergweg 10, D-06099 Halle (Saale) Germany. jens.boch@genetik.uni-halle.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19933107" target="_blank"〉PubMed〈/a〉
    Keywords: *Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/genetics ; Bacterial Proteins/chemistry/metabolism ; Base Pairing ; Base Sequence ; Biotechnology ; Capsicum/genetics ; DNA, Plant/*chemistry/*metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Genes, Plant ; Models, Biological ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Binding ; Repetitive Sequences, Amino Acid ; Tobacco/genetics ; Transcription Factors/chemistry/metabolism ; *Transcriptional Activation ; Xanthomonas/*metabolism/pathogenicity
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  • 88
    Publication Date: 2009-12-08
    Description: Nuclear export of microRNAs (miRNAs) by exportin-5 (Exp-5) is an essential step in miRNA biogenesis. Here, we present the 2.9 angstrom structure of the pre-miRNA nuclear export machinery formed by pre-miRNA complexed with Exp-5 and a guanine triphosphate (GTP)-bound form of the small nuclear guanine triphosphatase (GTPase) Ran (RanGTP). The x-ray structure shows that Exp-5:RanGTP recognizes the 2-nucleotide 3' overhang structure and the double-stranded stem of the pre-miRNA. Exp-5:RanGTP shields the pre-miRNA stem from degradation in a baseball mitt-like structure where it is held by broadly distributed weak interactions, whereas a tunnel-like structure of Exp-5 interacts strongly with the 2-nucleotide 3' overhang through hydrogen bonds and ionic interactions. RNA recognition by Exp-5:RanGTP does not depend on RNA sequence, implying that Exp-5:RanGTP can recognize a variety of pre-miRNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Chimari -- Yamashita, Eiki -- Lee, Soo Jae -- Shibata, Satoshi -- Katahira, Jun -- Nakagawa, Atsushi -- Yoneda, Yoshihiro -- Tsukihara, Tomitake -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1275-9. doi: 10.1126/science.1178705.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965479" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; Dogs ; Humans ; Hydrogen Bonding ; Karyopherins/*chemistry/metabolism ; MicroRNAs/*chemistry/metabolism ; Models, Molecular ; Nucleic Acid Conformation ; Physicochemical Processes ; Protein Conformation ; ran GTP-Binding Protein/chemistry/metabolism
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  • 89
    Publication Date: 2009-01-20
    Description: Bacterial multidrug tolerance is largely responsible for the inability of antibiotics to eradicate infections and is caused by a small population of dormant bacteria called persisters. HipA is a critical Escherichia coli persistence factor that is normally neutralized by HipB, a transcription repressor, which also regulates hipBA expression. Here, we report multiple structures of HipA and a HipA-HipB-DNA complex. HipA has a eukaryotic serine/threonine kinase-like fold and can phosphorylate the translation factor EF-Tu, suggesting a persistence mechanism via cell stasis. The HipA-HipB-DNA structure reveals the HipB-operator binding mechanism, approximately 70 degrees DNA bending, and unexpected HipA-DNA contacts. Dimeric HipB interacts with two HipA molecules to inhibit its kinase activity through sequestration and conformational inactivation. Combined, these studies suggest mechanisms for HipA-mediated persistence and its neutralization by HipB.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764309/" 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/PMC2764309/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schumacher, Maria A -- Piro, Kevin M -- Xu, Weijun -- Hansen, Sonja -- Lewis, Kim -- Brennan, Richard G -- AI048593/AI/NIAID NIH HHS/ -- GM061162/GM/NIGMS NIH HHS/ -- GM074815/GM/NIGMS NIH HHS/ -- R01 GM061162/GM/NIGMS NIH HHS/ -- R01 GM061162-09/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):396-401. doi: 10.1126/science.1163806.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of Texas, M. D. Anderson Cancer Center, Unit 1000, Houston, TX 77030, USA. maschuma@mdanderson.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19150849" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Crystallization ; Crystallography, X-Ray ; DNA, Bacterial/chemistry/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Dimerization ; *Drug Tolerance ; Escherichia coli/chemistry/*drug effects/genetics/*metabolism ; Escherichia coli Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Models, Molecular ; Nucleic Acid Conformation ; Operator Regions, Genetic ; Operon ; Peptide Elongation Factor Tu/metabolism ; Phosphorylation ; Protein Conformation ; Protein Folding ; Protein Kinase Inhibitors/metabolism ; Protein Kinases/chemistry/metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 90
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-04-04
    Description: A substantial challenge in engineering molecular motors is designing mechanisms to coordinate the motion between multiple domains of the motor so as to bias random thermal motion. For bipedal motors, this challenge takes the form of coordinating the movement of the biped's legs so that they can move in a synchronized fashion. To address this problem, we have constructed an autonomous DNA bipedal walker that coordinates the action of its two legs by cyclically catalyzing the hybridization of metastable DNA fuel strands. This process leads to a chemically ratcheted walk along a directionally polar DNA track. By covalently cross-linking aliquots of the walker to its track in successive walking states, we demonstrate that this Brownian motor can complete a full walking cycle on a track whose length could be extended for longer walks. We believe that this study helps to uncover principles behind the design of unidirectional devices that can function without intervention. This device should be able to fulfill roles that entail the performance of useful mechanical work on the nanometer scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470906/" 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/PMC3470906/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Omabegho, Tosan -- Sha, Ruojie -- Seeman, Nadrian C -- R37 GM029554/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 3;324(5923):67-71. doi: 10.1126/science.1170336.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19342582" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA/*chemistry ; DNA, Single-Stranded/*chemistry ; Furocoumarins/chemistry ; Inverted Repeat Sequences ; Nanotechnology/methods ; Nucleic Acid Conformation ; Nucleic Acid Denaturation ; Nucleic Acid Hybridization ; Ultraviolet Rays
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  • 91
    Publication Date: 2009-05-23
    Description: Integrons are found in the genome of hundreds of environmental bacteria but are mainly known for their role in the capture and spread of antibiotic resistance determinants among Gram-negative pathogens. We report a direct link between this system and the ubiquitous SOS response. We found that LexA controlled expression of most integron integrases and consequently regulated cassette recombination. This regulatory coupling enhanced the potential for cassette swapping and capture in cells under stress, while minimizing cassette rearrangements or loss in constant environments. This finding exposes integrons as integrated adaptive systems and has implications for antibiotic treatment policies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guerin, Emilie -- Cambray, Guillaume -- Sanchez-Alberola, Neus -- Campoy, Susana -- Erill, Ivan -- Da Re, Sandra -- Gonzalez-Zorn, Bruno -- Barbe, Jordi -- Ploy, Marie-Cecile -- Mazel, Didier -- New York, N.Y. -- Science. 2009 May 22;324(5930):1034. doi: 10.1126/science.1172914.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universite de Limoges, Faculte de Medecine, EA3175, INSERM, Equipe Avenir, 87000 Limoges, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19460999" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/metabolism ; Base Sequence ; Binding Sites ; Drug Resistance, Bacterial/genetics ; Escherichia coli/*genetics/metabolism ; Gene Expression Regulation, Bacterial ; Integrases/genetics ; Integrons/*genetics ; Molecular Sequence Data ; Promoter Regions, Genetic ; *Recombination, Genetic ; *SOS Response (Genetics) ; Serine Endopeptidases/metabolism ; Vibrio cholerae/*genetics/metabolism
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  • 92
    Publication Date: 2009-06-23
    Description: Amyloids are highly organized cross-beta-sheet-rich protein or peptide aggregates that are associated with pathological conditions including Alzheimer's disease and type II diabetes. However, amyloids may also have a normal biological function, as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation. We found that peptide and protein hormones in secretory granules of the endocrine system are stored in an amyloid-like cross-beta-sheet-rich conformation. Thus, functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865899/" 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/PMC2865899/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maji, Samir K -- Perrin, Marilyn H -- Sawaya, Michael R -- Jessberger, Sebastian -- Vadodaria, Krishna -- Rissman, Robert A -- Singru, Praful S -- Nilsson, K Peter R -- Simon, Rozalyn -- Schubert, David -- Eisenberg, David -- Rivier, Jean -- Sawchenko, Paul -- Vale, Wylie -- Riek, Roland -- P01 DK026741/DK/NIDDK NIH HHS/ -- P01 DK026741-29/DK/NIDDK NIH HHS/ -- P01 DK026741-30/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 17;325(5938):328-32. doi: 10.1126/science.1173155. Epub 2009 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Physical Chemistry, Eidgenossische Technische Hochschule (ETH) Zurich, Wolfgang-Paulistrasse 10, CH-8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19541956" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenocorticotropic Hormone/chemistry/metabolism ; Amyloid/*chemistry/metabolism ; Animals ; Cell Survival ; Corticotropin-Releasing Hormone/chemistry/metabolism ; Heparin, Low-Molecular-Weight/chemistry ; Humans ; Hydrogen-Ion Concentration ; Mice ; Neurons/cytology/physiology ; Peptide Hormones/*chemistry/metabolism ; Pituitary Gland/*chemistry ; Pituitary Gland, Anterior/chemistry/metabolism ; Pituitary Gland, Posterior/chemistry/metabolism ; Pituitary Hormones/*chemistry/metabolism ; Protein Conformation ; Rats ; Secretory Vesicles/*chemistry/metabolism ; Sheep ; Urocortins/chemistry/metabolism ; beta-Endorphin/chemistry/metabolism
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  • 93
    Publication Date: 2009-09-26
    Description: Metabolic plasticity, which largely relies on the creation of new genes, is an essential feature of plant adaptation and speciation and has led to the evolution of large gene families. A typical example is provided by the diversification of the cytochrome P450 enzymes in plants. We describe here a retroposition, neofunctionalization, and duplication sequence that, via selective and local amino acid replacement, led to the evolution of a novel phenolic pathway in Brassicaceae. This pathway involves a cascade of six successive hydroxylations by two partially redundant cytochromes P450, leading to the formation of N1,N5-di(hydroxyferuloyl)-N10-sinapoylspermidine, a major pollen constituent and so-far-overlooked player in phenylpropanoid metabolism. This example shows how positive Darwinian selection can favor structured clusters of nonsynonymous substitutions that are needed for the transition of enzymes to new functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuno, Michiyo -- Compagnon, Vincent -- Schoch, Guillaume A -- Schmitt, Martine -- Debayle, Delphine -- Bassard, Jean-Etienne -- Pollet, Brigitte -- Hehn, Alain -- Heintz, Dimitri -- Ullmann, Pascaline -- Lapierre, Catherine -- Bernier, Francois -- Ehlting, Jurgen -- Werck-Reichhart, Daniele -- New York, N.Y. -- Science. 2009 Sep 25;325(5948):1688-92. doi: 10.1126/science.1174095.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Biologie Moleculaire des Plantes, CNRS-UPR2357, Universite de Strasbourg, 28 Rue Goethe, 67083 Strasbourg Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779199" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/metabolism ; Base Sequence ; Brassica napus/genetics/growth & development/metabolism ; Brassicaceae/genetics/growth & development/*metabolism ; Cytochrome P-450 Enzyme System/chemistry/genetics/*metabolism ; *Evolution, Molecular ; Gene Duplication ; Hydroxylation ; Metabolic Networks and Pathways ; Methylation ; Models, Molecular ; Molecular Sequence Data ; Plant Proteins/chemistry/genetics/metabolism ; Pollen/*growth & development/metabolism ; RNA Interference ; Retroelements ; Selection, Genetic ; Spermidine/*analogs & derivatives/metabolism
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  • 94
    Publication Date: 2009-11-07
    Description: Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drmanac, Radoje -- Sparks, Andrew B -- Callow, Matthew J -- Halpern, Aaron L -- Burns, Norman L -- Kermani, Bahram G -- Carnevali, Paolo -- Nazarenko, Igor -- Nilsen, Geoffrey B -- Yeung, George -- Dahl, Fredrik -- Fernandez, Andres -- Staker, Bryan -- Pant, Krishna P -- Baccash, Jonathan -- Borcherding, Adam P -- Brownley, Anushka -- Cedeno, Ryan -- Chen, Linsu -- Chernikoff, Dan -- Cheung, Alex -- Chirita, Razvan -- Curson, Benjamin -- Ebert, Jessica C -- Hacker, Coleen R -- Hartlage, Robert -- Hauser, Brian -- Huang, Steve -- Jiang, Yuan -- Karpinchyk, Vitali -- Koenig, Mark -- Kong, Calvin -- Landers, Tom -- Le, Catherine -- Liu, Jia -- McBride, Celeste E -- Morenzoni, Matt -- Morey, Robert E -- Mutch, Karl -- Perazich, Helena -- Perry, Kimberly -- Peters, Brock A -- Peterson, Joe -- Pethiyagoda, Charit L -- Pothuraju, Kaliprasad -- Richter, Claudia -- Rosenbaum, Abraham M -- Roy, Shaunak -- Shafto, Jay -- Sharanhovich, Uladzislau -- Shannon, Karen W -- Sheppy, Conrad G -- Sun, Michel -- Thakuria, Joseph V -- Tran, Anne -- Vu, Dylan -- Zaranek, Alexander Wait -- Wu, Xiaodi -- Drmanac, Snezana -- Oliphant, Arnold R -- Banyai, William C -- Martin, Bruce -- Ballinger, Dennis G -- Church, George M -- Reid, Clifford A -- New York, N.Y. -- Science. 2010 Jan 1;327(5961):78-81. doi: 10.1126/science.1181498. Epub 2009 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, CA 94043, USA. rdrmanac@completegenomics.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19892942" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Computational Biology ; Costs and Cost Analysis ; DNA/*chemistry/genetics ; Databases, Nucleic Acid ; *Genome, Human ; Genomic Library ; Genotype ; Haplotypes ; Human Genome Project ; Humans ; Male ; *Microarray Analysis ; Nanostructures ; Nanotechnology ; Nucleic Acid Amplification Techniques ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/economics/instrumentation/*methods/standards ; Software
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  • 95
    Publication Date: 2008-02-23
    Description: The carboxysome is a bacterial microcompartment that functions as a simple organelle by sequestering enzymes involved in carbon fixation. The carboxysome shell is roughly 800 to 1400 angstroms in diameter and is assembled from several thousand protein subunits. Previous studies have revealed the three-dimensional structures of hexameric carboxysome shell proteins, which self-assemble into molecular layers that most likely constitute the facets of the polyhedral shell. Here, we report the three-dimensional structures of two proteins of previously unknown function, CcmL and OrfA (or CsoS4A), from the two known classes of carboxysomes, at resolutions of 2.4 and 2.15 angstroms. Both proteins assemble to form pentameric structures whose size and shape are compatible with formation of vertices in an icosahedral shell. Combining these pentamers with the hexamers previously elucidated gives two plausible, preliminary atomic models for the carboxysome shell.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanaka, Shiho -- Kerfeld, Cheryl A -- Sawaya, Michael R -- Cai, Fei -- Heinhorst, Sabine -- Cannon, Gordon C -- Yeates, Todd O -- New York, N.Y. -- Science. 2008 Feb 22;319(5866):1083-6. doi: 10.1126/science.1151458.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18292340" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/physiology ; Crystallography, X-Ray ; Cytoplasmic Structures/*chemistry/ultrastructure ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Synechocystis/*chemistry/ultrastructure
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  • 96
    Publication Date: 2008-01-26
    Description: We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibson, Daniel G -- Benders, Gwynedd A -- Andrews-Pfannkoch, Cynthia -- Denisova, Evgeniya A -- Baden-Tillson, Holly -- Zaveri, Jayshree -- Stockwell, Timothy B -- Brownley, Anushka -- Thomas, David W -- Algire, Mikkel A -- Merryman, Chuck -- Young, Lei -- Noskov, Vladimir N -- Glass, John I -- Venter, J Craig -- Hutchison, Clyde A 3rd -- Smith, Hamilton O -- New York, N.Y. -- Science. 2008 Feb 29;319(5867):1215-20. doi: 10.1126/science.1151721. Epub 2008 Jan 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉J. Craig Venter Institute, Rockville, MD 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18218864" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Chromosomes, Artificial, Bacterial ; Chromosomes, Artificial, Yeast ; *Cloning, Molecular ; DNA, Bacterial/*chemical synthesis ; DNA, Recombinant ; Escherichia coli/genetics ; Genetic Vectors ; *Genome, Bacterial ; Genomics/*methods ; Mycoplasma genitalium/*genetics ; Oligodeoxyribonucleotides/chemical synthesis ; Plasmids ; Recombination, Genetic ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, DNA ; Transformation, Genetic
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  • 97
    Publication Date: 2008-01-12
    Description: The analysis of natural contact interfaces between protein subunits and between proteins has disclosed some general rules governing their association. We have applied these rules to produce a number of novel assemblies, demonstrating that a given protein can be engineered to form contacts at various points of its surface. Symmetry plays an important role because it defines the multiplicity of a designed contact and therefore the number of required mutations. Some of the proteins needed only a single side-chain alteration in order to associate to a higher-order complex. The mobility of the buried side chains has to be taken into account. Four assemblies have been structurally elucidated. Comparisons between the designed contacts and the results will provide useful guidelines for the development of future architectures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grueninger, Dirk -- Treiber, Nora -- Ziegler, Mathias O P -- Koetter, Jochen W A -- Schulze, Monika-Sarah -- Schulz, Georg E -- New York, N.Y. -- Science. 2008 Jan 11;319(5860):206-9. doi: 10.1126/science.1150421.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Organische Chemie und Biochemie, Albert-Ludwigs-Universitat, Albertstrasse 21, 79104 Freiburg im Breisgau, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18187656" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehyde-Lyases/*chemistry/genetics ; Bacterial Proteins/*chemistry/genetics ; Crystallization ; Crystallography, X-Ray ; Cysteine Synthase/*chemistry/genetics ; Dimerization ; Glycoside Hydrolases/*chemistry/genetics ; Models, Molecular ; Mutagenesis, Site-Directed ; Mutant Proteins/chemistry ; Point Mutation ; Porins/*chemistry/genetics ; Protein Conformation ; *Protein Engineering ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/*chemistry/genetics ; Urocanate Hydratase/*chemistry/genetics
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  • 98
    Publication Date: 2008-11-29
    Description: Altered abundance of several intrinsically unstructured proteins (IUPs) has been associated with perturbed cellular signaling that may lead to pathological conditions such as cancer. Therefore, it is important to understand how cells precisely regulate the availability of IUPs. We observed that regulation of transcript clearance, proteolytic degradation, and translational rate contribute to controlling the abundance of IUPs, some of which are present in low amounts and for short periods of time. Abundant phosphorylation and low stochasticity in transcription and translation indicate that the availability of IUPs can be finely tuned. Fidelity in signaling may require that most IUPs be available in appropriate amounts and not present longer than needed.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803065/" 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/PMC2803065/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gsponer, Jorg -- Futschik, Matthias E -- Teichmann, Sarah A -- Babu, M Madan -- G0600158/Medical Research Council/United Kingdom -- MC_U105161047/Medical Research Council/United Kingdom -- MC_U105185859/Medical Research Council/United Kingdom -- U.1051.04.027.00001.01 (85859)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Nov 28;322(5906):1365-8. doi: 10.1126/science.1163581.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. jgsponer@mrc-lmb.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19039133" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Cycle ; Computational Biology ; Genes, Fungal ; Humans ; Phosphorylation ; Protein Biosynthesis ; Protein Conformation ; Protein Kinases/metabolism ; Proteome/chemistry ; RNA, Fungal/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Saccharomyces cerevisiae/chemistry/cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; Schizosaccharomyces pombe Proteins/chemistry/metabolism ; Signal Transduction ; Transcription, Genetic
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  • 99
    Publication Date: 2008-04-19
    Description: Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3-ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3-ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3-ECD C-terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin-1 receptor (TIR) domains. The overall shape of the TLR3-ECD does not change upon binding to dsRNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761030/" 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/PMC2761030/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Lin -- Botos, Istvan -- Wang, Yan -- Leonard, Joshua N -- Shiloach, Joseph -- Segal, David M -- Davies, David R -- Z01 BC009254-33/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2008 Apr 18;320(5874):379-81. doi: 10.1126/science.1155406.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18420935" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Dimerization ; Humans ; Ligands ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/metabolism ; NF-kappa B/metabolism ; Nucleic Acid Conformation ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Double-Stranded/*chemistry/*metabolism ; *Signal Transduction ; Toll-Like Receptor 3/*chemistry/genetics/*metabolism
    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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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-02-16
    Description: Cadherin-mediated cell adhesion and signaling is essential for metazoan development and yet is absent from all other multicellular organisms. We found cadherin genes at numbers similar to those observed in complex metazoans in one of the closest single-celled relatives of metazoans, the choanoflagellate Monosiga brevicollis. Because the evolution of metazoans from a single-celled ancestor required novel cell adhesion and signaling mechanisms, the discovery of diverse cadherins in choanoflagellates suggests that cadherins may have contributed to metazoan origins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abedin, Monika -- King, Nicole -- New York, N.Y. -- Science. 2008 Feb 15;319(5865):946-8. doi: 10.1126/science.1151084.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology and Center for Integrative Genomics, University of California at Berkeley, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276888" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Cadherins/*chemistry/*genetics/physiology ; Cell Adhesion ; Ciona intestinalis/chemistry ; Cnidaria/chemistry ; Drosophila melanogaster/chemistry ; Eukaryota/*chemistry ; Eukaryotic Cells/*chemistry/physiology ; Mice ; Molecular Sequence Data ; Protein Structure, Tertiary ; Repetitive Sequences, Amino Acid ; Signal Transduction ; Tyrosine/metabolism ; src Homology Domains
    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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