View source for 7dng


==DARPin 63_B7 in complex with linear V3-crown (MN) peptide==
<StructureSection load='7dng' size='340' side='right'caption='[[7dng]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7dng]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DNG 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]] 1.42&#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=7dng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dng OCA], [https://pdbe.org/7dng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dng RCSB], [https://www.ebi.ac.uk/pdbsum/7dng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dng ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base. Challenging this view, we present V3-crown directed broadly neutralizing Designed Ankyrin Repeat Proteins (bnDs) matching the breadth of V3-base bnAbs. While most bnAbs target prefusion Env, V3-crown bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve breadth by focusing on highly conserved residues that are accessible in two distinct V3 conformations, one of which resembles CCR5-bound V3. We further show that these V3-crown conformations can, in principle, be attacked by antibodies. Supporting this conclusion, analysis of antibody binding activity in the Swiss 4.5 K HIV-1 cohort (n = 4,281) revealed a co-evolution of V3-crown reactivities and neutralization breadth. Our results indicate a role of V3-crown responses and its conformational preferences in bnAb development to be considered in preventive and therapeutic approaches.

Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.,Friedrich N, Stiegeler E, Glogl M, Lemmin T, Hansen S, Kadelka C, Wu Y, Ernst P, Maliqi L, Foulkes C, Morin M, Eroglu M, Liechti T, Ivan B, Reinberg T, Schaefer JV, Karakus U, Ursprung S, Mann A, Rusert P, Kouyos RD, Robinson JA, Gunthard HF, Pluckthun A, Trkola A Nat Commun. 2021 Nov 18;12(1):6705. doi: 10.1038/s41467-021-27075-0. PMID:34795280<ref>PMID:34795280</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dng" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Plueckthun A]]
[[Category: Wu Y]]