View source for 6u59


==HIV-1 B41 SOSIP.664 in complex with rabbit antibody 13B==
<SX load='6u59' size='340' side='right' viewer='molstar' caption='[[6u59]], [[Resolution|resolution]] 3.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6u59]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U59 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]] 3.86&#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=6u59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u59 OCA], [https://pdbe.org/6u59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u59 RCSB], [https://www.ebi.ac.uk/pdbsum/6u59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u59 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B3UES2_9HIV1 B3UES2_9HIV1] 
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== Publication Abstract from PubMed ==
Extensive studies with subtype A BG505-derived HIV Env immunogens have revealed that the dominant autologous neutralizing epitope in rabbits is located in an exposed region of the heavily glycosylated trimer that lacks potential N-linked glycosylation sites at positions 230, 241, and 289. The Env derived from B41, a subtype B virus, shares a glycan hole centered on positions 230 and 289. To test whether broader neutralization to the common glycan hole can be achieved, we immunized rabbits with B41 SOSIP alone, as well as B41 and BG505 co-immunization. We isolated autologous neutralizing antibodies (nAbs) and described their structure in complex with the B41 Env. Our data suggest that distinct autologous nAb lineages are induced by BG505 and B41 immunogens, even when both were administered together. In contrast to previously described BG505 glycan hole antibodies, the B41-specific nAbs accommodate the &gt;97% conserved N241 glycan, which is present in B41. Single particle cryo-electron microscopy studies confirmed that B41 and BG505-specific nAbs bind to overlapping glycan hole epitopes. We then used our high-resolution data to guide mutations in the BG505 glycan hole epitope in an attempt to broaden the reactivity of a B41-specific nAb, but only recovered partial binding. Our data demonstrate that lack of cross-reactivity in glycan hole antibodies is due to amino acid differences within the epitope and our attempts to rationally design cross-reactive trimers resulted in only limited success. Thus, even for the immunodominant glycan hole shared between BG505 and B41 the prospect of designing prime-boost immunogens remains difficult.IMPORTANCE A glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer immunized rabbits. Our high-resolution cryoEM studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that even for the immunodominant glycan hole shared between BG505 and B41 the prospect of designing prime-boost immunogens remains difficult.

Autologous neutralizing antibody responses to an HIV envelope glycan hole are not easily broadened in rabbits.,Yang YR, McCoy LE, van Gils MJ, Andrabi R, Turner HL, Yuan M, Cottrell CA, Ozorowski G, Voss J, Pauthner M, Polveroni TM, Messmer T, Wilson IA, Sanders RW, Burton DR, Ward AB J Virol. 2020 Jan 15. pii: JVI.01861-19. doi: 10.1128/JVI.01861-19. PMID:31941772<ref>PMID:31941772</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 6u59" style="background-color:#fffaf0;"></div>

==See Also==
*[[Gp120 3D structures|Gp120 3D structures]]
*[[Gp41 3D Structures|Gp41 3D Structures]]
== References ==
<references/>
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</SX>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Ward AB]]
[[Category: Yang YR]]