View source for 6nf5


==BG505 MD64 N332-GT5 SOSIP trimer in complex with BG18-like precursor HMP1 fragmentantigen binding and base-binding RM20A3 fragment antigen binding==
<SX load='6nf5' size='340' side='right' viewer='molstar' caption='[[6nf5]], [[Resolution|resolution]] 3.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nf5]] is a 18 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/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NF5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NF5 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]] 3.71&#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=6nf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nf5 OCA], [https://pdbe.org/6nf5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nf5 RCSB], [https://www.ebi.ac.uk/pdbsum/6nf5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nf5 ProSAT]</span></td></tr>
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== 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 ==
Vaccine induction of broadly neutralizing antibodies (bnAbs) to human immunodeficiency virus (HIV) remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity determining region 3 (HCDR3) is a major barrier. Exploiting ultra-deep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model, and in ex-vivo screens bound a range of potential bnAb-precursor human naive B cells. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs, and could be applied to most HCDR3-dominant antibodies from other pathogens.

A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.,Steichen JM, Lin YC, Havenar-Daughton C, Pecetta S, Ozorowski G, Willis JR, Toy L, Sok D, Liguori A, Kratochvil S, Torres JL, Kalyuzhniy O, Melzi E, Kulp DW, Raemisch S, Hu X, Bernard SM, Georgeson E, Phelps N, Adachi Y, Kubitz M, Landais E, Umotoy J, Robinson A, Briney B, Wilson IA, Burton DR, Ward AB, Crotty S, Batista FD, Schief WR Science. 2019 Oct 31. pii: science.aax4380. doi: 10.1126/science.aax4380. PMID:31672916<ref>PMID:31672916</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Gp41 3D Structures|Gp41 3D Structures]]
== References ==
<references/>
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</SX>
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Macaca mulatta]]
[[Category: Ozorowski G]]
[[Category: Schief WR]]
[[Category: Steichen JM]]
[[Category: Torres JL]]
[[Category: Ward AB]]