7lo6
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Structure of CD4 mimetic BNM-III-170 in complex with BG505 SOSIP.664 HIV-1 Env trimer and 17b Fab== |
| - | <StructureSection load='7lo6' size='340' side='right'caption='[[7lo6]]' scene=''> | + | <StructureSection load='7lo6' size='340' side='right'caption='[[7lo6]], [[Resolution|resolution]] 3.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7lo6]] 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=7LO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LO6 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=7lo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lo6 OCA], [https://pdbe.org/7lo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lo6 RCSB], [https://www.ebi.ac.uk/pdbsum/7lo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lo6 ProSAT]</span></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]] 3.9Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5VG:~{N}-[(1~{R},2~{R})-2-(CARBAMIMIDAMIDOMETHYL)-5-(METHYLAMINOMETHYL)-2,3-DIHYDRO-1~{H}-INDEN-1-YL]-~{N}-(4-CHLORANYL-3-FLUORANYL-PHENYL)ETHANEDIAMIDE'>5VG</scene>, <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=7lo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lo6 OCA], [https://pdbe.org/7lo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lo6 RCSB], [https://www.ebi.ac.uk/pdbsum/7lo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lo6 ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions of people. Entry into target cells is mediated by the HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4's Phe43 interaction with Env by inserting into the conserved Phe43 pocket on Env subunit gp120. Here, we present single-particle cryo-EM structures of CD4-mimetics BNM-III-170 and M48U1 bound to a BG505 native-like Env trimer plus the CD4-induced antibody 17b at 3.7 A and 3.9 A resolution, respectively. CD4-mimetic-bound BG505 exhibits canonical CD4-induced conformational changes including trimer opening, formation of the 4-stranded gp120 bridging sheet, displacement of the V1V2 loop, and formation of a compact and elongated gp41 HR1C helical bundle. We conclude that CD4-induced structural changes on both gp120 and gp41 Env subunits are induced by binding to the gp120 Phe43 pocket. | ||
| + | |||
| + | Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation.,Jette CA, Barnes CO, Kirk SM, Melillo B, Smith AB 3rd, Bjorkman PJ Nat Commun. 2021 Mar 29;12(1):1950. doi: 10.1038/s41467-021-21816-x. PMID:33782388<ref>PMID:33782388</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7lo6" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Gp120 3D structures|Gp120 3D structures]] | ||
| + | *[[Gp41 3D Structures|Gp41 3D Structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Bjorkman PJ]] |
| + | [[Category: Jette CA]] | ||
Current revision
Structure of CD4 mimetic BNM-III-170 in complex with BG505 SOSIP.664 HIV-1 Env trimer and 17b Fab
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