8jen: Difference between revisions

(One intermediate revision by the same user not shown)

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 8jen is ~~ON HOLD until Paper~~ Publication

==Crystal structure of TIGIT in complexed with Ociperlimab, crystal form II==

== Structural highlights ==

<table><tr><td colspan='2'>[[8jen]] is a 12 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=8JEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JEN 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]] 2.71Å</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=8jen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jen OCA], [https://pdbe.org/8jen PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jen RCSB], [https://www.ebi.ac.uk/pdbsum/8jen PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jen 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.

== 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.

~~Authors:~~ Sun, J., Zhang, X.X., ~~Song, J~~.

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>

~~Description~~: ~~Crystal structure of TIGIT in complexed with Ociperlimab, crystal form II~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

[[Category: Song, J]]

[[Category: Sun, J]]

== References ==

[[Category: Zhang~~, X.X~~]]

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Song J]]

[[Category: Sun J]]

[[Category: Zhang XX]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8jen is ON HOLD  until Paper Publication
+==Crystal structure of TIGIT in complexed with Ociperlimab, crystal form II==
+<StructureSection load='8jen' size='340' side='right'caption='[[8jen]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jen]] is a 12 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=8JEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JEN 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]] 2.71&#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=8jen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jen OCA], [https://pdbe.org/8jen PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jen RCSB], [https://www.ebi.ac.uk/pdbsum/8jen PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jen 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.
-Authors: Sun, J., Zhang, X.X., Song, J.
+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>
-Description: Crystal structure of TIGIT in complexed with Ociperlimab, crystal form II
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Song, J]]
+<div class="pdbe-citations 8jen" style="background-color:#fffaf0;"></div>
-[[Category: Sun, J]]
+== References ==
-[[Category: Zhang, X.X]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Song J]]
+[[Category: Sun J]]
+[[Category: Zhang XX]]