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| | <SX load='6udj' size='340' side='right' viewer='molstar' caption='[[6udj]], [[Resolution|resolution]] 2.50Å' scene=''> | | <SX load='6udj' size='340' side='right' viewer='molstar' caption='[[6udj]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6udj]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UDJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6udj]] is a 18 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=6UDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UDJ FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">env ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6udj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6udj OCA], [http://pdbe.org/6udj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6udj RCSB], [http://www.ebi.ac.uk/pdbsum/6udj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6udj ProSAT]</span></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=6udj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6udj OCA], [https://pdbe.org/6udj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6udj RCSB], [https://www.ebi.ac.uk/pdbsum/6udj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6udj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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] | + | [https://www.uniprot.org/uniprot/S6B2B6_HUMAN S6B2B6_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6udj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6udj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Gp120 3D structures|Gp120 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | + | [[Category: Human immunodeficiency virus 1]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Abernathy, M E]] | + | [[Category: Abernathy ME]] |
| - | [[Category: Barnes, C O]] | + | [[Category: Barnes CO]] |
| - | [[Category: Bjorkman, P J]] | + | [[Category: Bjorkman PJ]] |
| - | [[Category: Gristick, H B]] | + | [[Category: Gristick HB]] |
| - | [[Category: Bnab]]
| + | |
| - | [[Category: Cryo-em]]
| + | |
| - | [[Category: Env]]
| + | |
| - | [[Category: Hiv-1 broadly neutralizing antibody]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
Function
S6B2B6_HUMAN
Publication Abstract from PubMed
Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 mug/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-A cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.
Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody.,Schommers P, Gruell H, Abernathy ME, Tran MK, Dingens AS, Gristick HB, Barnes CO, Schoofs T, Schlotz M, Vanshylla K, Kreer C, Weiland D, Holtick U, Scheid C, Valter MM, van Gils MJ, Sanders RW, Vehreschild JJ, Cornely OA, Lehmann C, Fatkenheuer G, Seaman MS, Bloom JD, Bjorkman PJ, Klein F Cell. 2020 Feb 6;180(3):471-489.e22. doi: 10.1016/j.cell.2020.01.010. Epub 2020, Jan 30. PMID:32004464[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schommers P, Gruell H, Abernathy ME, Tran MK, Dingens AS, Gristick HB, Barnes CO, Schoofs T, Schlotz M, Vanshylla K, Kreer C, Weiland D, Holtick U, Scheid C, Valter MM, van Gils MJ, Sanders RW, Vehreschild JJ, Cornely OA, Lehmann C, Fatkenheuer G, Seaman MS, Bloom JD, Bjorkman PJ, Klein F. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell. 2020 Feb 6;180(3):471-489.e22. doi: 10.1016/j.cell.2020.01.010. Epub 2020, Jan 30. PMID:32004464 doi:http://dx.doi.org/10.1016/j.cell.2020.01.010
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