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==Model of the HIV-1 gp41 membrane-proximal external region, transmembrane domain and cytoplasmic tail (LLP2)== | ==Model of the HIV-1 gp41 membrane-proximal external region, transmembrane domain and cytoplasmic tail (LLP2)== | ||
<StructureSection load='6ujv' size='340' side='right'caption='[[6ujv]]' scene=''> | <StructureSection load='6ujv' size='340' side='right'caption='[[6ujv]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full | <table><tr><td colspan='2'>[[6ujv]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UJV FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ujv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ujv OCA], [http://pdbe.org/6ujv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ujv RCSB], [http://www.ebi.ac.uk/pdbsum/6ujv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ujv ProSAT]</span></td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jyn|5jyn]], [[6e8w|6e8w]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ujv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ujv OCA], [http://pdbe.org/6ujv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ujv RCSB], [http://www.ebi.ac.uk/pdbsum/6ujv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ujv ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/A0A060KRW4_9HIV1 A0A060KRW4_9HIV1]] Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.[HAMAP-Rule:MF_04083] Surface protein gp120: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells.[HAMAP-Rule:MF_04083] Transmembrane protein gp41: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm.[HAMAP-Rule:MF_04083] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The prefusion conformation of HIV-1 envelope protein (Env) is recognized by most broadly neutralizing antibodies (bnAbs). Studies showed that alterations of its membrane-related components, including the transmembrane domain (TMD) and cytoplasmic tail (CT), can reshape the antigenic structure of the Env ectodomain. Using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of an Env segment encompassing the TMD and a large portion of the CT in bicelles. The structure reveals that the CT folds into amphipathic helices that wrap around the C-terminal end of the TMD, thereby forming a support baseplate for the rest of Env. NMR dynamics measurements provide evidences of dynamic coupling across the TMD between the ectodomain and CT. Pseudovirus-based neutralization assays suggest that CT-TMD interaction preferentially affects antigenic structure near the apex of the Env trimer. These results explain why the CT can modulate the Env antigenic properties and may facilitate HIV-1 Env-based vaccine design. | |||
Structural basis of transmembrane coupling of the HIV-1 envelope glycoprotein.,Piai A, Fu Q, Cai Y, Ghantous F, Xiao T, Shaik MM, Peng H, Rits-Volloch S, Chen W, Seaman MS, Chen B, Chou JJ Nat Commun. 2020 May 8;11(1):2317. doi: 10.1038/s41467-020-16165-0. PMID:32385256<ref>PMID:32385256</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ujv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cai Y]] | [[Category: Cai, Y]] | ||
[[Category: Chen B]] | [[Category: Chen, B]] | ||
[[Category: Chen W]] | [[Category: Chen, W]] | ||
[[Category: Chou | [[Category: Chou, J J]] | ||
[[Category: Fu Q]] | [[Category: Fu, Q]] | ||
[[Category: Ghantous F]] | [[Category: Ghantous, F]] | ||
[[Category: Liu Z]] | [[Category: Liu, Z]] | ||
[[Category: Peng H]] | [[Category: Peng, H]] | ||
[[Category: Piai A]] | [[Category: Piai, A]] | ||
[[Category: Rits-Volloch S]] | [[Category: Rits-Volloch, S]] | ||
[[Category: Seaman | [[Category: Seaman, M S]] | ||
[[Category: Shaik | [[Category: Shaik, M M]] | ||
[[Category: Xiao T]] | [[Category: Xiao, T]] | ||
[[Category: Cytoplasmic tail]] | |||
[[Category: Membrane protein]] | |||
[[Category: Membrane-proximal external region]] | |||
[[Category: Transmembrane domain]] | |||
[[Category: Viral protein]] | |||