View source for 6kvf


==Structure of anti-hCXCR2 abN48 in complex with its CXCR2 epitope==
<StructureSection load='6kvf' size='340' side='right'caption='[[6kvf]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kvf]] is a 6 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=6KVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KVF 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]] 2.79&#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=6kvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kvf OCA], [https://pdbe.org/6kvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kvf RCSB], [https://www.ebi.ac.uk/pdbsum/6kvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kvf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CXCR2_HUMAN CXCR2_HUMAN] Autosomal recessive severe congenital neutropenia due to CXCR2 deficiency. 
== Function ==
[https://www.uniprot.org/uniprot/CXCR2_HUMAN CXCR2_HUMAN] Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Receptors and their ligands are important therapeutic targets for about one third of marketed drugs. Here, we describe an epitope-guided approach for selection of antibodies that modulate cellular signaling of targeted receptors. We chose CXC chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as receptor and a CXCR2 N-terminal peptide for antibody selection. We obtain a highly selective, tight-binding antibody from a 10(11)-member antibody library using combinatorial enrichment. Structural and Hydrogen-Deuterium-Exchange mass spectrometry analyses demonstrate antibody interaction with an N-terminal region of CXCR2 that is part of the IL-8 epitope. The antibody strongly inhibits IL-8-induced and CXCR2-mediated neutrophil chemotaxis in vitro and alleviates hCXCR2-dependent experimental autoimmune encephalomyelitis symptoms in mice. As inappropriate neutrophil migration accompanies many diseases including inflammatory bowel disease, glomerulonephritis, allergic asthma, chronic obstructive pulmonary disease, and cancer, this antibody has potential for development as a therapeutic agent, akin to anti-TNF antibodies. However, an important difference here is that the antibody targets the chemokine receptor and competes with natural ligand, rather than targeting the ligand itself.

Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms.,Shi X, Wan Y, Wang N, Xiang J, Wang T, Yang X, Wang J, Dong X, Dong L, Yan L, Li Y, Liu L, Hou S, Zhong Z, Wilson IA, Yang B, Yang G, Lerner RA Nat Commun. 2021 May 5;12(1):2547. doi: 10.1038/s41467-021-22810-z. PMID:33953162<ref>PMID:33953162</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kvf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wilson IA]]
[[Category: Xiang JC]]
[[Category: Yan L]]
[[Category: Yang B]]