6v8x: Difference between revisions

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==VRC01 Bound BG505 F14 HIV-1 SOSIP Envelope Trimer Structure==
==VRC01 Bound BG505 F14 HIV-1 SOSIP Envelope Trimer Structure==
<StructureSection load='6v8x' size='340' side='right'caption='[[6v8x]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<SX load='6v8x' size='340' side='right' viewer='molstar' caption='[[6v8x]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6v8x]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V8X FirstGlance]. <br>
<table><tr><td colspan='2'>[[6v8x]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V8X FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</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=6v8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v8x OCA], [http://pdbe.org/6v8x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v8x RCSB], [http://www.ebi.ac.uk/pdbsum/6v8x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v8x ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6v8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v8x OCA], [https://pdbe.org/6v8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v8x RCSB], [https://www.ebi.ac.uk/pdbsum/6v8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v8x ProSAT]</span></td></tr>
</table>
</table>
== Function ==
<div style="background-color:#fffaf0;">
[[http://www.uniprot.org/uniprot/Q2N0S6_9HIV1 Q2N0S6_9HIV1]] The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447]  The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).[SAAS:SAAS000328_004_240990]  
== Publication Abstract from PubMed ==
The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to prevent CD4-induced rearrangements in the HIV-1 BG505 Env trimer. Binding analysis and single-molecule Forster Resonance Energy Transfer confirm that these mutations prevent CD4-induced transitions of the HIV-1 Env. Structural analysis by single-particle cryo-electron microscopy performed on the BG505 SOSIP mutant Env proteins shows rearrangements in the gp120 topological layer contacts with gp41. Displacement of a conserved tryptophan (W571) from its typical pocket in these Env mutants renders the Env insensitive to CD4 binding. These results reveal the critical function of W571 as a conformational switch in Env allostery and receptor-mediated viral entry and provide insights on Env conformation that are relevant for vaccine design.
 
Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.,Henderson R, Lu M, Zhou Y, Mu Z, Parks R, Han Q, Hsu AL, Carter E, Blanchard SC, Edwards RJ, Wiehe K, Saunders KO, Borgnia MJ, Bartesaghi A, Mothes W, Haynes BF, Acharya P, Munir Alam S Nat Commun. 2020 Jan 24;11(1):520. doi: 10.1038/s41467-019-14196-w. PMID:31980614<ref>PMID:31980614</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6v8x" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Gp120 3D structures|Gp120 3D structures]]
*[[Gp41 3D Structures|Gp41 3D Structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</SX>
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Acharya, P]]
[[Category: Acharya P]]
[[Category: Henderson, R]]
[[Category: Henderson R]]
[[Category: Complex]]
[[Category: Hiv-1]]
[[Category: Immunogen]]
[[Category: Trimer]]
[[Category: Viral protein-immune system complex]]

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