3nte: Difference between revisions
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==Crystal Structure of the Wild-type Full-Length HIV-1 Capsid Protein== | ==Crystal Structure of the Wild-type Full-Length HIV-1 Capsid Protein== | ||
<StructureSection load='3nte' size='340' side='right' caption='[[3nte]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='3nte' size='340' side='right' caption='[[3nte]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=I3M:TRI-IODODE+ANION'>I3M</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=I3M:TRI-IODODE+ANION'>I3M</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA, gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA, gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nte OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nte RCSB], [http://www.ebi.ac.uk/pdbsum/3nte PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nte OCA], [http://pdbe.org/3nte PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nte RCSB], [http://www.ebi.ac.uk/pdbsum/3nte PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nte ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3nte" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 14:42, 5 August 2016
Crystal Structure of the Wild-type Full-Length HIV-1 Capsid ProteinCrystal Structure of the Wild-type Full-Length HIV-1 Capsid Protein
Structural highlights
Function[Q77YG1_9HIV1] Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers (By similarity).[SAAS:SAAS012344_004_011858] Publication Abstract from PubMedThe capsid (CA) protein plays crucial roles in HIV infection and replication, essential to viral maturation. The absence of high-resolution structural data on unassembled CA hinders the development of antivirals effective in inhibiting assembly. Unlike enzymes that have targetable, functional substrate-binding sites, the CA does not have a known site that affects catalytic or other innate activity, which can be more readily targeted in drug development efforts. We report the crystal structure of the HIV-1 CA, revealing the domain organization in the context of the wild-type full-length (FL) unassembled CA. The FL CA adopts an antiparallel dimer configuration, exhibiting a domain organization sterically incompatible with capsid assembly. A small compound, generated in situ during crystallization, is bound tightly at a hinge site ("H site"), indicating that binding at this interdomain region stabilizes the ADP conformation. Electron microscopy studies on nascent crystals reveal both dimeric and hexameric lattices coexisting within a single condition, in agreement with the interconvertibility of oligomeric forms and supporting the feasibility of promoting assembly-incompetent dimeric states. Solution characterization in the presence of the H-site ligand shows predominantly unassembled dimeric CA, even under conditions that promote assembly. Our structure elucidation of the HIV-1 FL CA and characterization of a potential allosteric binding site provides three-dimensional views of an assembly-defective conformation, a state targeted in, and thus directly relevant to, inhibitor development. Based on our findings, we propose an unprecedented means of preventing CA assembly, by "conformationally trapping" CA in assembly-incompetent conformational states induced by H-site binding. Structure of the HIV-1 full-length capsid protein in a conformationally trapped unassembled state induced by small-molecule binding.,Du S, Betts L, Yang R, Shi H, Concel J, Ahn J, Aiken C, Zhang P, Yeh JI J Mol Biol. 2011 Feb 25;406(3):371-86. doi: 10.1016/j.jmb.2010.11.027. Epub 2010 , Dec 10. PMID:21146540[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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