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==Crystal structure of the non-neutralizing and ADCC-potent C11-like antibody N12-i3 in complex with HIV-1 clade A/E gp120, the CD4 mimetic M48U1, and the antibody N5-i5.== | ==Crystal structure of the non-neutralizing and ADCC-potent C11-like antibody N12-i3 in complex with HIV-1 clade A/E gp120, the CD4 mimetic M48U1, and the antibody N5-i5.== | ||
<StructureSection load='5w4l' size='340' side='right' caption='[[5w4l]], [[Resolution|resolution]] 2.92Å' scene=''> | <StructureSection load='5w4l' size='340' side='right'caption='[[5w4l]], [[Resolution|resolution]] 2.92Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5w4l]] is a 12 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5w4l]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W4L FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.92Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=MPT:BETA-MERCAPTOPROPIONIC+ACID'>MPT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=U2X:O-(CYCLOHEXYLMETHYL)-L-TYROSINE'>U2X</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=5w4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w4l OCA], [https://pdbe.org/5w4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w4l RCSB], [https://www.ebi.ac.uk/pdbsum/5w4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w4l ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0M3KKW9_9HIV1 A0A0M3KKW9_9HIV1] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 22: | ||
==See Also== | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Gp120 3D structures|Gp120 3D structures]] | |||
*[[3D structures of human antibody|3D structures of human antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: | [[Category: Gohain N]] | ||
[[Category: | [[Category: Pazgier M]] | ||
[[Category: | [[Category: Tolbert WD]] | ||
Latest revision as of 17:07, 4 October 2023
Crystal structure of the non-neutralizing and ADCC-potent C11-like antibody N12-i3 in complex with HIV-1 clade A/E gp120, the CD4 mimetic M48U1, and the antibody N5-i5.Crystal structure of the non-neutralizing and ADCC-potent C11-like antibody N12-i3 in complex with HIV-1 clade A/E gp120, the CD4 mimetic M48U1, and the antibody N5-i5.
Structural highlights
FunctionPublication Abstract from PubMedAntibodies can have an impact on HIV-1 infection in multiple ways, including antibody-dependent cellular cytotoxicity (ADCC), a correlate of protection observed in the RV144 vaccine trial. One of the most potent ADCC-inducing epitopes on HIV-1 Env is recognized by the C11 antibody. Here, we present the crystal structure, at 2.9 A resolution, of the C11-like antibody N12-i3, in a quaternary complex with the HIV-1 gp120, a CD4-mimicking peptide M48U1, and an A32-like antibody, N5-i5. Antibody N12-i3 recognizes an epitope centered on the N-terminal "eighth strand" of a critical beta sandwich, which our analysis indicates to be emblematic of a late-entry state, after the gp120 detachment. In prior entry states, this sandwich comprises only seven strands, with the eighth strand instead pairing with a portion of the gp120 C terminus. The conformational gymnastics of HIV-1 gp120 thus includes altered beta-strand pairing, possibly to reduce immunogenicity, although nevertheless still recognized by the human immune system. Targeting the Late Stage of HIV-1 Entry for Antibody-Dependent Cellular Cytotoxicity: Structural Basis for Env Epitopes in the C11 Region.,Tolbert WD, Gohain N, Alsahafi N, Van V, Orlandi C, Ding S, Martin L, Finzi A, Lewis GK, Ray K, Pazgier M Structure. 2017 Nov 7;25(11):1719-1731.e4. doi: 10.1016/j.str.2017.09.009. Epub, 2017 Oct 19. PMID:29056481[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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