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2me4

From Proteopedia

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Current revision

HIV-1 gp41 clade C Membrane Proximal External Region peptide in DPC micelle

Structural highlights

2me4 is a 1 chain structure with sequence from Human immunodeficiency virus 1. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q27Q69_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).

Publication Abstract from PubMed

HIV-1 (human immunodeficiency virus type 1) uses its trimeric gp160 envelope (Env) protein consisting of non-covalently associated gp120 and gp41 subunits to mediate entry into human T lymphocytes. A facile virus fusion mechanism compensates for the sparse Env copy number observed on viral particles and includes a 22-amino-acid, lentivirus-specific adaptation at the gp41 base (amino acid residues 662-683), termed the membrane proximal external region (MPER). We show by NMR and EPR that MPER consists of a structurally conserved pair of viral lipid-immersed helices separated by a hinge with tandem joints that can be locked by capping residues between helices. This design fosters efficient HIV-1 fusion via interconverting structures while, at the same time, affording immune escape. Disruption of both joints by double alanine mutations at Env positions 671 and 674 (AA) results in attenuation of Env-mediated cell-cell fusion and hemifusion, as well as viral infectivity mediated by both CD4-dependent and CD4-independent viruses. The potential mechanism of disruption was revealed by structural analysis of MPER conformational changes induced by AA mutation. A deeper acyl chain-buried MPER middle section and the elimination of cross-hinge rigid-body motion almost certainly impede requisite structural rearrangements during the fusion process, explaining the absence of MPER AA variants among all known naturally occurring HIV-1 viral sequences. Furthermore, those broadly neutralization antibodies directed against the HIV-1 MPER exploit the tandem joint architecture involving helix capping, thereby disrupting hinge function.

Disruption of Helix-Capping Residues 671 and 674 Reveals a Role in HIV-1 Entry for a Specialized Hinge Segment of the Membrane Proximal External Region of gp41.,Sun ZY, Cheng Y, Kim M, Song L, Choi J, Kudahl UJ, Brusic V, Chowdhury B, Yu L, Seaman MS, Bellot G, Shih WM, Wagner G, Reinherz EL J Mol Biol. 2013 Sep 26. pii: S0022-2836(13)00614-1. doi:, 10.1016/j.jmb.2013.09.030. PMID:24075869^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sun ZY, Cheng Y, Kim M, Song L, Choi J, Kudahl UJ, Brusic V, Chowdhury B, Yu L, Seaman MS, Bellot G, Shih WM, Wagner G, Reinherz EL. Disruption of Helix-Capping Residues 671 and 674 Reveals a Role in HIV-1 Entry for a Specialized Hinge Segment of the Membrane Proximal External Region of gp41. J Mol Biol. 2013 Sep 26. pii: S0022-2836(13)00614-1. doi:, 10.1016/j.jmb.2013.09.030. PMID:24075869 doi:http://dx.doi.org/10.1016/j.jmb.2013.09.030

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2me4"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2me4]] 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=2ME4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ME4 FirstGlance]. <br>
-</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=2me4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2me4 OCA], [https://pdbe.org/2me4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2me4 RCSB], [https://www.ebi.ac.uk/pdbsum/2me4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2me4 ProSAT]</span></td></tr>
+</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=2me4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2me4 OCA], [https://pdbe.org/2me4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2me4 RCSB], [https://www.ebi.ac.uk/pdbsum/2me4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2me4 ProSAT]</span></td></tr>
 </table>
 == Function ==

2me4

From Proteopedia

Current revision

HIV-1 gp41 clade C Membrane Proximal External Region peptide in DPC micelle

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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