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==Structural Analysis of the Unmutated Ancestor of the HIV-1 Envelope V2 Region Antibody CH58 Isolated From an RV144 HIV-1 Vaccine Efficacy Trial Vaccinee and Associated with Decreased Transmission Risk==
<StructureSection load='4ris' size='340' side='right'caption='[[4ris]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ris]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RIS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RIS 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]] 2.3&#8491;</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=4ris FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ris OCA], [https://pdbe.org/4ris PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ris RCSB], [https://www.ebi.ac.uk/pdbsum/4ris PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ris ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q70966_9HIV1 Q70966_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human monoclonal antibody CH58 isolated from an RV144 vaccinee binds at Lys169 of the HIV-1 Env gp120 V2 region, a site of vaccine-induced immune pressure. CH58 neutralizes HIV-1 CRF_01 AE strain 92TH023 and mediates ADCC against CD4 + T cell targets infected with CRF_01 AE tier 2 virus. CH58 and other antibodies that bind to a gp120 V2 epitope have a second light chain complementarity determining region (LCDR2) bearing a glutamic acid, aspartic acid (ED) motif involved in forming salt bridges with polar, basic side amino acid side chains in V2. In an effort to learn how V2 responses develop, we determined the crystal structures of the CH58-UA antibody unliganded and bound to V2 peptide. The structures showed an LCDR2 structurally pre-conformed from germline to interact with V2 residue Lys169. LCDR3 was subject to conformational selection through the affinity maturation process. Kinetic analyses demonstrate that only a few contacts were responsible for a 2000-fold increase in KD through maturation, and this effect was predominantly due to an improvement in off-rate. This study shows that preconformation and preconfiguration can work in concert to produce antibodies with desired immunogenic properties.

Structural analysis of the unmutated ancestor of the HIV-1 envelope V2 region antibody CH58 isolated from an RV144 vaccine efficacy trial vaccinee.,Nicely NI, Wiehe K, Kepler TB, Jaeger FH, Dennison SM, Rerks-Ngarm S, Nitayaphan S, Pitisuttithum P, Kaewkungwal J, Robb ML, O'Connell RJ, Michael NL, Kim JH, Liao HX, Munir Alam S, Hwang KK, Bonsignori M, Haynes BF EBioMedicine. 2015 Jun 20;2(7):713-22. doi: 10.1016/j.ebiom.2015.06.016., eCollection 2015 Jul. PMID:26288844<ref>PMID:26288844</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ris" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Alam SM]]
[[Category: Bonsignori M]]
[[Category: Dennison SM]]
[[Category: Haynes BF]]
[[Category: Hwang K-K]]
[[Category: Jaeger FH]]
[[Category: Kaewkungwal J]]
[[Category: Kepler TB]]
[[Category: Kim JH]]
[[Category: Liao H-X]]
[[Category: Michael NL]]
[[Category: Nicely NI]]
[[Category: Nitayaphan S]]
[[Category: O'Connell RJ]]
[[Category: Pitisuttithum P]]
[[Category: Rerks-Ngarm S]]
[[Category: Robb ML]]
[[Category: Wiehe K]]