View source for 7lpn


==Cryo-EM structure of llama J3 VHH antibody in complex with HIV-1 Env BG505 DS-SOSIP.664==
<StructureSection load='7lpn' size='340' side='right'caption='[[7lpn]], [[Resolution|resolution]] 3.61&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lpn]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LPN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LPN 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]] 3.61&#8491;</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'>[https://proteopedia.org/fgij/fg.htm?mol=7lpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lpn OCA], [https://pdbe.org/7lpn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lpn RCSB], [https://www.ebi.ac.uk/pdbsum/7lpn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lpn 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]
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== Publication Abstract from PubMed ==
Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies (J3, A12, C8, and D7), all of which targeted the CD4-binding site, in complex with the HIV-1 envelope (Env) gp120 core, and determined a cryoelectron microscopy (cryo-EM) structure of J3 with the Env trimer. Crystal and cryo-EM structures of J3 complexes revealed this nanobody to mimic binding to the prefusion-closed trimer for the primary site of CD4 recognition as well as a secondary quaternary site. In contrast, crystal structures of A12, C8, and D7 with gp120 revealed epitopes that included portions of the gp120 inner domain, inaccessible on the prefusion-closed trimer. Overall, these structures explain the broad and potent neutralization of J3 and limited neutralization of A12, C8, and D7, which utilized binding modes incompatible with the neutralization-targeted prefusion-closed conformation of Env.

Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.,Zhou T, Chen L, Gorman J, Wang S, Kwon YD, Lin BC, Louder MK, Rawi R, Stancofski ED, Yang Y, Zhang B, Quigley AF, McCoy LE, Rutten L, Verrips T, Weiss RA, Doria-Rose NA, Shapiro L, Kwong PD Structure. 2022 Jun 2;30(6):862-875.e4. doi: 10.1016/j.str.2022.03.012. Epub 2022 , Apr 11. PMID:35413243<ref>PMID:35413243</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7lpn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Gp120 3D structures|Gp120 3D structures]]
*[[Gp41 3D Structures|Gp41 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Gorman J]]
[[Category: Kwong PD]]