9d74: Difference between revisions
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==CryoEM structure of anti-MHC-I Fab B1.23.2 complex with HLA-B44:05== | |||
<StructureSection load='9d74' size='340' side='right'caption='[[9d74]], [[Resolution|resolution]] 3.31Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9d74]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=9D74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9D74 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.31Å</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=9d74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9d74 OCA], [https://pdbe.org/9d74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9d74 RCSB], [https://www.ebi.ac.uk/pdbsum/9d74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9d74 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q860B7_HUMAN Q860B7_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Anti-major histocompatibility complex class I (MHC-I) mAbs can stimulate immune responses to tumors and infections by blocking suppressive signals delivered via various immune inhibitory receptors. To understand such functions, we determined the structure of a highly cross-reactive anti-human MHC-I mAb, B1.23.2, in complex with the MHC-I molecule HLA-B*44:05 by both cryo-electron microscopy (cryo-EM) and X-ray crystallography. Structural models determined by the two methods were essentially identical revealing that B1.23.2 binds a conserved region on the alpha2(1) helix that overlaps the killer immunoglobulin-like receptor (KIR) binding site. Structural comparison to KIR/HLA complexes reveals a mechanism by which B1.23.2 blocks inhibitory receptor interactions, leading to natural killer (NK) cell activation. B1.23.2 treatment of the human KLM-1 pancreatic cancer model in humanized (NSG-IL15) mice provides evidence of suppression of tumor growth. Such anti-MHC-I mAb that block inhibitory KIR/HLA interactions may prove useful for tumor immunotherapy. | |||
Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity.,Jiang J, Panda AK, Natarajan K, Lei H, Sharma S, Boyd LF, Towler RR, Chempati S, Ahmad J, Morton AJ, Lang ZC, Sun Y, Sgourakis N, Meier-Schellersheim M, Huang RK, Shevach EM, Margulies DH Commun Biol. 2026 Feb 2. doi: 10.1038/s42003-026-09641-8. PMID:41629525<ref>PMID:41629525</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9d74" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Jiang | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Huang R]] | |||
[[Category: Jiang J]] | |||
[[Category: Lei H]] | |||
[[Category: Margulies DH]] | |||
[[Category: Natarajan K]] | |||
Latest revision as of 07:10, 11 February 2026
CryoEM structure of anti-MHC-I Fab B1.23.2 complex with HLA-B44:05
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