7mkc: Difference between revisions
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<StructureSection load='7mkc' size='340' side='right'caption='[[7mkc]], [[Resolution|resolution]] 2.65Å' scene=''> | <StructureSection load='7mkc' size='340' side='right'caption='[[7mkc]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MKC FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1B0:N-METHYL-NALPHA-[(2-METHYL-1H-INDOL-3-YL)ACETYL]-N-PHENYL-L-PHENYLALANINAMIDE'>1B0</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1B0:N-METHYL-NALPHA-[(2-METHYL-1H-INDOL-3-YL)ACETYL]-N-PHENYL-L-PHENYLALANINAMIDE'>1B0</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7mkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mkc OCA], [https://pdbe.org/7mkc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mkc RCSB], [https://www.ebi.ac.uk/pdbsum/7mkc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mkc ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7mkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mkc OCA], [https://pdbe.org/7mkc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mkc RCSB], [https://www.ebi.ac.uk/pdbsum/7mkc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mkc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Kirby KA]] | [[Category: Kirby KA]] | ||
[[Category: Sarafianos SG]] | [[Category: Sarafianos SG]] | ||
Latest revision as of 09:34, 21 November 2024
N74D mutant of the HIV-1 capsid protein in complex with PF-3450074 (PF74)N74D mutant of the HIV-1 capsid protein in complex with PF-3450074 (PF74)
Structural highlights
Publication Abstract from PubMedThe core of HIV-1 viruses bearing the capsid change N74D (HIV-1-N74D) do not bind the human protein CPSF6. In primary human CD4(+) T cells, HIV-1-N74D viruses exhibit an infectivity defect when compared to wild-type. We first investigated whether loss of CPSF6 binding accounts for the loss of infectivity. Depletion of CPSF6 in human CD4(+) T cells did not affect the early stages of wild-type HIV-1 replication, suggesting that defective infectivity in the case of HIV-1-N74D viruses is not due to the loss of CPSF6 binding. Based on our previous result that cyclophilin A (Cyp A) protected HIV-1 from human tripartite motif-containing protein 5alpha (TRIM5alphahu) restriction in CD4(+) T cells, we found that depletion of TRIM5alphahu in CD4(+) T cells rescued the infectivity of HIV-1-N74D, suggesting that HIV-1-N74D cores interacted with TRIM5alphahu. Accordingly, TRIM5alphahu binding to HIV-1-N74D cores was increased compared with that of wild-type cores, and consistently, HIV-1-N74D cores lost their ability to bind Cyp A. In agreement with the notion that N74D capsids are defective in their ability to bind Cyp A, we found that HIV-1-N74D viruses were 20-fold less sensitive to TRIMCyp restriction when compared to wild-type viruses in OMK cells. Structural analysis revealed that N74D hexameric capsid protein in complex with PF74 is different from wild-type hexameric capsid protein in complex with PF74, which explains the defect of N74D capsids to interact with Cyp A. In conclusion, we showed that the decreased infectivity of HIV-1-N74D in CD4(+) T cells is due to a loss of Cyp A protection from TRIM5alphahu restriction activity. TRIM5alpha Restriction of HIV-1-N74D Viruses in Lymphocytes Is Caused by a Loss of Cyclophilin A Protection.,Selyutina A, Simons LM, Kirby KA, Bulnes-Ramos A, Hu P, Sarafianos SG, Hultquist JF, Diaz-Griffero F Viruses. 2022 Feb 10;14(2). pii: v14020363. doi: 10.3390/v14020363. PMID:35215956[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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