View source for 4rnr


==Crystal structure of broadly neutralizing anti-HIV antibody PGT130==
<StructureSection load='4rnr' size='340' side='right'caption='[[4rnr]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rnr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RNR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RNR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.758&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4rnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rnr OCA], [https://pdbe.org/4rnr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rnr RCSB], [https://www.ebi.ac.uk/pdbsum/4rnr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rnr ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The high-mannose patch of HIV envelope (Env) elicits broadly neutralizing antibodies (bnAbs) during natural infection relatively frequently and consequently this region has become a major target of vaccine design. However, it has also become clear that antibody recognition of the region is complex due to the quaternary nature of the bnAb epitopes and variability in neighboring loops and glycans critical to the epitopes. BnAbs against this region have some shared and some distinguishing features that are crucial to understand in order to design optimal immunogens that can induce different classes of bnAbs against this region. Here, we compare two branches of a single antibody lineage, in which all members recognize the high-mannose patch. One branch (prototype bnAb PGT128) has a 6-amino acid insertion in CDRH2 that is crucial for broad neutralization. Antibodies in this branch appear to favor a glycan site at N332 on gp120 and somatic hypermutation is required to accommodate the neighboring V1 loop glycans and glycan heterogeneity. The other branch (prototype bnAb PGT130) lacks the CDRH2 insertion. Antibodies in this branch are noticeably effective at neutralizing viruses with an alternate N334 glycan site but are less able to accommodate glycan heterogeneity. We identify a new somatic variant within this branch that is predominantly dependent on N334. The crystal structure of PGT130 offers some insight into these differences compared to PGT128. We conclude that different immunogens may be required to elicit bnAbs that have the optimal characteristics of the two branches of the lineage described. IMPORTANCE: Development of an HIV vaccine is of vital importance for control of new infections and it is thought that elicitation of HIV bnAbs will be an important component of an effective vaccine. Increasingly, bnAbs that bind to the cluster of high-mannose glycans on the HIV envelope glycoprotein, gp120, are being highlighted as important templates for vaccine design. In particular, bnAbs from donor 36 (PGTs125-131) have been shown to be extremely broad and potent. Combination of these bnAbs enhanced neutralization breadth considerably suggesting that an optimal immunogen should elicit several antibodies from this family. Here we study the evolution of this antibody family to inform immunogen design. We identify two classes of bnAb that differ in their recognition of the high-mannose patch and show that different immunogens may be required to elicit these different classes.

Two classes of broadly neutralizing antibodies within a single lineage directed to the high-mannose patch of HIV Envelope.,Doores KJ, Kong L, Krumm SA, Le KM, Sok D, Laserson U, Garces F, Poignard P, Wilson IA, Burton DR J Virol. 2014 Nov 5. pii: JVI.02905-14. PMID:25378488<ref>PMID:25378488</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kong L]]
[[Category: Wilson IA]]