View source for 6cez


==Crystal Structure of Rabbit Anti-HIV-1 gp120 V2 Fab 16C2 in complex with V2 peptide ConB==
<StructureSection load='6cez' size='340' side='right'caption='[[6cez]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cez]] is a 3 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=6CEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CEZ 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]] 2.399&#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=6cez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cez OCA], [https://pdbe.org/6cez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cez RCSB], [https://www.ebi.ac.uk/pdbsum/6cez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cez ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin alpha4beta7, a gut-homing receptor. Using both cell-surface expressed alpha4beta7 and a soluble alpha4beta7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of alpha4beta7 in a cation -sensitive manner and is inhibited by soluble MAdCAM. Thus, V2 mimics MAdCAM in the way that it binds to alpha4beta7, providing HIV a potential mechanism to discriminate between functionally distinct subsets of lymphocytes, including those with gut-homing potential. Furthermore, alpha4beta7 antagonists developed for the treatment of inflammatory bowel diseases, block V2 binding to alpha4beta7. A 15-amino acid V2 -derived peptide is sufficient to mediate binding to alpha4beta7. It includes the canonical LDV/I alpha4beta7 binding site, a cryptic epitope that lies 7-9 amino acids amino terminal to the LDV/I, and residues K169 and I181. These two residues were identified in a sieve analysis of the RV144 vaccine trial as sites of vaccine -mediated immune pressure. HIV and SIV V2 mAbs elicited by both vaccination and infection that recognize this peptide block V2-alpha4beta7 interactions. These mAbs recognize conformations absent from the beta- barrel presented in a stabilized HIV SOSIP gp120/41 trimer. The mimicry of MAdCAM-alpha4beta7 interactions by V2 may influence early events in HIV infection, particularly the rapid seeding of gut tissues, and supports the view that HIV replication in gut tissue is a central feature of HIV pathogenesis.

Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to alpha4beta7.,Lertjuthaporn S, Cicala C, Van Ryk D, Liu M, Yolitz J, Wei D, Nawaz F, Doyle A, Horowitch B, Park C, Lu S, Lou Y, Wang S, Pan R, Jiang X, Villinger F, Byrareddy SN, Santangelo PJ, Morris L, Wibmer CK, Biris K, Mason RD, Gorman J, Hiatt J, Martinelli E, Roederer M, Fujikawa D, Gorini G, Franchini G, Arakelyan A, Ansari AA, Pattanapanyasat K, Kong XP, Fauci AS, Arthos J PLoS Pathog. 2018 Aug 28;14(8):e1007278. doi: 10.1371/journal.ppat.1007278., eCollection 2018 Aug. PMID:30153309<ref>PMID:30153309</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 6cez" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Gp120 3D structures|Gp120 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Kong X]]
[[Category: Pan R]]