7sd3: Difference between revisions
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The | ==Cytoplasmic tail deleted HIV-1 Env bound with three 4E10 Fabs== | ||
<StructureSection load='7sd3' size='340' side='right'caption='[[7sd3]], [[Resolution|resolution]] 3.67Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7sd3]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/HIV_whole-genome_vector_AA1305#18 HIV whole-genome vector AA1305#18] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SD3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SD3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.67Å</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=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=7sd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sd3 OCA], [https://pdbe.org/7sd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sd3 RCSB], [https://www.ebi.ac.uk/pdbsum/7sd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sd3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Vaccines targeting HIV-1's gp160 spike protein are stymied by high viral mutation rates and structural chicanery. gp160's membrane-proximal external region (MPER) is the target of naturally arising broadly neutralizing antibodies (bnAbs), yet MPER-based vaccines fail to generate bnAbs. Here, nanodisc-embedded spike protein was investigated by cryo-electron microscopy and molecular-dynamics simulations, revealing spontaneous ectodomain tilting that creates vulnerability for HIV-1. While each MPER protomer radiates centrally towards the three-fold axis contributing to a membrane-associated tripod structure that is occluded in the upright spike, tilting provides access to the opposing MPER. Structures of spike proteins with bound 4E10 bnAb Fabs reveal that the antibody binds exposed MPER, thereby altering MPER dynamics, modifying average ectodomain tilt, and imposing strain on the viral membrane and the spike's transmembrane segments, resulting in the abrogation of membrane fusion and informing future vaccine development. | |||
Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack.,Yang S, Hiotis G, Wang Y, Chen J, Wang JH, Kim M, Reinherz EL, Walz T Nat Commun. 2022 Oct 27;13(1):6393. doi: 10.1038/s41467-022-34008-y. PMID:36302771<ref>PMID:36302771</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7sd3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Gp120 3D structures|Gp120 3D structures]] | |||
*[[Gp41 3D Structures|Gp41 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: HIV whole-genome vector AA1305#18]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Walz T]] | |||
[[Category: Yang S]] | |||