8x6b
Crystal structure of immune receptor PVRIG in complex with ligand Nectin-2
Structural highlights
FunctionPVRIG_HUMAN Cell surface receptor for NECTIN2. May act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals. Following interaction with NECTIN2, inhibits T-cell proliferation. Competes with CD226 for NECTIN2-binding.[1] Publication Abstract from PubMedNectin and nectin-like (Necl) co-receptor axis, comprised of receptors DNAM-1, TIGIT, CD96, PVRIG, and nectin/Necl ligands, is gaining prominence in immuno-oncology. Within this axis, the inhibitory receptor PVRIG recognizes Nectin-2 with high affinity, but the underlying molecular basis remains unknown. By determining the crystal structure of PVRIG in complex with Nectin-2, we identified a unique CC' loop in PVRIG, which complements the double-lock-and-key binding mode and contributes to its high affinity for Nectin-2. The association of the corresponding charged residues in the F-strands explains the ligand selectivity of PVRIG toward Nectin-2 but not for Necl-5. Moreover, comprehensive comparisons of the binding capacities between co-receptors and ligands provide innovative insights into the intra-axis immunoregulatory mechanism. Taken together, these findings broaden our understanding of immune recognition and regulation mediated by nectin/Necl co-receptors and provide a rationale for the development of immunotherapeutic strategies targeting the nectin/Necl axis. Structural basis for the immune recognition and selectivity of the immune receptor PVRIG for ligand Nectin-2.,Hu S, Han P, Wang M, Cao X, Liu H, Zhang S, Zhang S, Liu J, Han Y, Xiao J, Chen Q, Miao K, Qi J, Tan S, Gao GF, Wang H Structure. 2024 Apr 8:S0969-2126(24)00094-7. doi: 10.1016/j.str.2024.03.012. PMID:38626767[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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