7wg3: Difference between revisions
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==Structural basis of interleukin-17B receptor in complex with a neutralizing antibody D9 for guiding humanization and affinity maturation for cancer therapy== | |||
<StructureSection load='7wg3' size='340' side='right'caption='[[7wg3]], [[Resolution|resolution]] 2.19Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7wg3]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WG3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WG3 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7wg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wg3 OCA], [https://pdbe.org/7wg3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wg3 RCSB], [https://www.ebi.ac.uk/pdbsum/7wg3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wg3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A3KN55_BOVIN A3KN55_BOVIN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Upregulation of interleukin-17 receptor B (IL-17RB) is known to be oncogenic, while other IL-17 receptors and ligands are generally involved in pro-inflammatory pathways. We identify a mouse neutralizing monoclonal antibody (mAb) D9, which blocks the IL-17RB/IL-17B pathway and inhibits pancreatic tumorigenesis in an orthotopic mouse model. The X-ray crystal structure of the IL-17RB ectodomain in complex with its neutralizing antibody D9 shows that D9 binds to a predicted ligand binding interface and engages with the A'-A loop of IL-17RB fibronectin III domain 1 in a unique conformational state. This structure also provides important paratope information to guide the design of antibody humanization and affinity maturation of D9, resulting in a humanized 1B12 antibody with marginal affinity loss and effective neutralization of IL-17B/IL-17RB signaling to impede tumorigenesis in a mouse xenograft model. | |||
Structural basis of interleukin-17B receptor in complex with a neutralizing antibody for guiding humanization and affinity maturation.,Lee WH, Chen X, Liu IJ, Lee JH, Hu CM, Wu HC, Wang SK, Lee WH, Ma C Cell Rep. 2022 Oct 25;41(4):111555. doi: 10.1016/j.celrep.2022.111555. PMID:36288706<ref>PMID:36288706</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7wg3" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Chen XR]] | |||
[[Category: Hu CM]] | |||
[[Category: Lee JH]] | |||
[[Category: Lee WH]] | |||
[[Category: Liu IJ]] | |||
[[Category: Ma C]] | |||
[[Category: Wang SK]] | |||
[[Category: Wu HC]] | |||
Revision as of 07:25, 9 November 2022
Structural basis of interleukin-17B receptor in complex with a neutralizing antibody D9 for guiding humanization and affinity maturation for cancer therapy
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