8jeo
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 8jeo is ON HOLD Authors: Jian, J.S., Xiangxiang, X.Z., Jing, J.S. Description: Crystal structure of TIGIT in complexed with Tiragolumab [[Category:...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of TIGIT in complexed with Tiragolumab== | |
| + | <StructureSection load='8jeo' size='340' side='right'caption='[[8jeo]], [[Resolution|resolution]] 2.06Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8jeo]] 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=8JEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JEO 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]] 2.06Å</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=8jeo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jeo OCA], [https://pdbe.org/8jeo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jeo RCSB], [https://www.ebi.ac.uk/pdbsum/8jeo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jeo ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TIGIT_HUMAN TIGIT_HUMAN] Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | TIGIT is mainly expressed on T cells and is an inhibitory checkpoint receptor that binds to its ligand PVR in the tumor microenvironment. Anti-TIGIT monoclonal antibodies (mAbs) such as Ociperlimab and Tiragolumab block the TIGIT-PVR interaction and are in clinical development. However, the molecular blockade mechanism of these mAbs remains elusive. Here, we report the crystal structures of TIGIT in complex with Ociperlimab_Fab and Tiragolumab_Fab revealing that both mAbs bind TIGIT with a large steric clash with PVR. Furthermore, several critical epitopic residues are identified. Interestingly, the binding affinity of Ociperlimab toward TIGIT increases approximately 17-fold when lowering the pH from 7.4 to 6.0. Our structure shows a strong electrostatic interaction between ASP103(HCDR3) and HIS76(TIGIT) explaining the pH-responsive mechanism of Ociperlimab. In contrast, Tiragolumab does not show an acidic pH-dependent binding enhancement. Our results provide valuable information that could help to improve the efficacy of therapeutic antibodies for cancer treatment. | ||
| - | + | Structural insights into the unique pH-responsive characteristics of the anti-TIGIT therapeutic antibody Ociperlimab.,Sun J, Zhang X, Xue L, Cheng L, Zhang J, Chen X, Shen Z, Li K, Wang L, Huang C, Song J Structure. 2024 May 2;32(5):550-561.e5. doi: 10.1016/j.str.2024.02.009. Epub 2024 , Mar 8. PMID:38460520<ref>PMID:38460520</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8jeo" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Song J]] | ||
| + | [[Category: Sun J]] | ||
| + | [[Category: Zhang XX]] | ||
Current revision
Crystal structure of TIGIT in complexed with Tiragolumab
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