8szy

Crystal Structure of Heterotrimeric Anti-TIGIT Fabs in complex with human TIGIT

spinqualitylabelsall models 8szy, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8szy is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.31Å Ligands: NAG, PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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 The clinical successes of immune checkpoint blockade have invigorated efforts to activate T cell-mediated responses against cancer. Targeting members of the PVR family, consisting of inhibitory receptors TIGIT, CD96, and CD112R, has been an active area of clinical investigation. In this study, the binding interactions and molecular assemblies of the PVR family receptors and ligands have been assessed in vitro. Furthermore, the anti-TIGIT monoclonal antibody BMS-986207 crystal structure in complex with TIGIT was determined and shows that the antibody binds an epitope that is commonly targeted by the CD155 ligand as well as other clinical anti-TIGIT antibodies. In contrast to previously proposed models, where TIGIT outcompetes costimulatory receptor CD226 for binding to CD155 due to much higher affinity (nanomolar range), our data rather suggest that PVR family members all engage in interactions with relatively weak affinity (micromolar range), including TIGIT and CD155 interactions. Thus, TIGIT and other PVR inhibitory receptors likely elicit immune suppression via increased surface expression rather than inherent differences in affinity. This work provides an improved foundational understanding of the PVR family network and mechanistic insight into therapeutic antibody intervention. Biophysical characterization of PVR family interactions and therapeutic antibody recognition to TIGIT.,Diong SJ, Jashnani A, Drake AW, Bee C, Findeisen F, Dollinger G, Wang F, Rajpal A, Strop P, Lee PS MAbs. 2023 Jan-Dec;15(1):2253788. doi: 10.1080/19420862.2023.2253788. PMID:37675979 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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