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==The structure of the V3 region within gp120 of JR-FL HIV-1 strain (minimized average structure)== | |||
<StructureSection load='2esx' size='340' side='right'caption='[[2esx]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2esx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ESX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ESX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2esx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2esx OCA], [https://pdbe.org/2esx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2esx RCSB], [https://www.ebi.ac.uk/pdbsum/2esx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2esx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/O36236_9HIV1 O36236_9HIV1] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HIV-1 coreceptor usage plays a critical role in virus tropism and pathogenesis. A switch from CCR5- to CXCR4-using viruses occurs during the course of HIV-1 infection and correlates with subsequent disease progression. A single mutation at position 322 within the V3 loop of the HIV-1 envelope glycoprotein gp120, from a negatively to a positively charged residue, was found to be sufficient to switch an R5 virus to an X4 virus. In this study, the NMR structure of the V3 region of an R5 strain, HIV-1(JR-FL), in complex with an HIV-1-neutralizing antibody was determined. Positively charged and negatively charged residues at positions 304 and 322, respectively, oppose each other in the beta-hairpin structure, enabling a favorable electrostatic interaction that stabilizes the postulated R5 conformation. Comparison of the R5 conformation with the postulated X4 conformation of the V3 region (positively charged residue at position 322) reveals that electrostatic repulsion between residues 304 and 322 in X4 strains triggers the observed one register shift in the N-terminal strand of the V3 region. We posit that electrostatic interactions at the base of the V3 beta-hairpin can modulate the conformation and thereby influence the phenotype switch. In addition, we suggest that interstrand cation-pi interactions between positively charged and aromatic residues induce the switch to the X4 conformation as a result of the S306R mutation. The existence of three pairs of identical (or very similar) amino acids in the V3 C-terminal strand facilitates the switch between the R5 and X4 conformations. | |||
Molecular switch for alternative conformations of the HIV-1 V3 region: implications for phenotype conversion.,Rosen O, Sharon M, Quadt-Akabayov SR, Anglister J Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13950-5. Epub 2006 Sep 11. PMID:16966601<ref>PMID:16966601</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2esx" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Gp120 3D structures|Gp120 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Anglister | [[Category: Anglister J]] | ||
[[Category: Quadt | [[Category: Quadt SR]] | ||
[[Category: Rosen | [[Category: Rosen O]] | ||
[[Category: Samson | [[Category: Samson AO]] | ||
[[Category: Sharon | [[Category: Sharon M]] | ||
Latest revision as of 19:35, 13 December 2023
The structure of the V3 region within gp120 of JR-FL HIV-1 strain (minimized average structure)The structure of the V3 region within gp120 of JR-FL HIV-1 strain (minimized average structure)
Structural highlights
FunctionPublication Abstract from PubMedHIV-1 coreceptor usage plays a critical role in virus tropism and pathogenesis. A switch from CCR5- to CXCR4-using viruses occurs during the course of HIV-1 infection and correlates with subsequent disease progression. A single mutation at position 322 within the V3 loop of the HIV-1 envelope glycoprotein gp120, from a negatively to a positively charged residue, was found to be sufficient to switch an R5 virus to an X4 virus. In this study, the NMR structure of the V3 region of an R5 strain, HIV-1(JR-FL), in complex with an HIV-1-neutralizing antibody was determined. Positively charged and negatively charged residues at positions 304 and 322, respectively, oppose each other in the beta-hairpin structure, enabling a favorable electrostatic interaction that stabilizes the postulated R5 conformation. Comparison of the R5 conformation with the postulated X4 conformation of the V3 region (positively charged residue at position 322) reveals that electrostatic repulsion between residues 304 and 322 in X4 strains triggers the observed one register shift in the N-terminal strand of the V3 region. We posit that electrostatic interactions at the base of the V3 beta-hairpin can modulate the conformation and thereby influence the phenotype switch. In addition, we suggest that interstrand cation-pi interactions between positively charged and aromatic residues induce the switch to the X4 conformation as a result of the S306R mutation. The existence of three pairs of identical (or very similar) amino acids in the V3 C-terminal strand facilitates the switch between the R5 and X4 conformations. Molecular switch for alternative conformations of the HIV-1 V3 region: implications for phenotype conversion.,Rosen O, Sharon M, Quadt-Akabayov SR, Anglister J Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13950-5. Epub 2006 Sep 11. PMID:16966601[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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