8X6B

Crystal structure of immune receptor PVRIG in complex with ligand Nectin-2

Summary for 8X6B

• Entry DOI: 10.2210/pdb8x6b/pdb
• Descriptor: Transmembrane protein PVRIG, Nectin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 28771.39

Authors

Hu, S.T.,Han, P.,Wang, H.,Qi, J.X. (deposition date: 2023-11-21, release date: 2024-04-24, Last modification date: 2024-11-13)

Primary citation

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, G.F.,Wang, H.
Structural basis for the immune recognition and selectivity of the immune receptor PVRIG for ligand Nectin-2.
Structure, 32:918-929.e4, 2024

PubMed Abstract: Nectin 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.

PubMed: 38626767
DOI: 10.1016/j.str.2024.03.012

Experimental method

X-RAY DIFFRACTION (2 Å)