View source for 4nhg


==Crystal Structure of 2G12 IgG Dimer==
<StructureSection load='4nhg' size='340' side='right'caption='[[4nhg]], [[Resolution|resolution]] 8.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nhg]] is a 18 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=4NHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NHG 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]] 8.001&#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=4nhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nhg OCA], [https://pdbe.org/4nhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nhg RCSB], [https://www.ebi.ac.uk/pdbsum/4nhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nhg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6PYX1_HUMAN Q6PYX1_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human immunoglobulin G (IgG) 2G12 recognizes high-mannose carbohydrates on the HIV type 1 (HIV-1) envelope glycoprotein gp120. Its two antigen-binding fragments (Fabs) are intramolecularly domain exchanged, resulting in a rigid (Fab)2 unit including a third antigen-binding interface not found in antibodies with flexible Fab arms. We determined crystal structures of dimeric 2G12 IgG created by intermolecular domain exchange, which exhibits increased breadth and &gt;50-fold increased neutralization potency compared with monomeric 2G12. The four Fab and two fragment crystalline (Fc) regions of dimeric 2G12 were localized at low resolution in two independent structures, revealing IgG dimers with two (Fab)2 arms analogous to the Fabs of conventional monomeric IgGs. Structures revealed three conformationally distinct dimers, demonstrating flexibility of the (Fab)2-Fc connections that was confirmed by electron microscopy, small-angle X-ray scattering, and binding studies. We conclude that intermolecular domain exchange, flexibility, and bivalent binding to allow avidity effects are responsible for the increased potency and breadth of dimeric 2G12.

Structural basis for enhanced HIV-1 neutralization by a dimeric immunoglobulin G form of the glycan-recognizing antibody 2G12.,Wu Y, West AP Jr, Kim HJ, Thornton ME, Ward AB, Bjorkman PJ Cell Rep. 2013 Dec 12;5(5):1443-55. doi: 10.1016/j.celrep.2013.11.015. Epub 2013 , Dec 5. PMID:24316082<ref>PMID:24316082</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4nhg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bjorkman PJ]]
[[Category: Kim HJ]]
[[Category: Thornton ME]]
[[Category: Ward AB]]
[[Category: West Jr AP]]
[[Category: Wu Y]]