8X6B

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

8X6B の概要

• エントリーDOI: 10.2210/pdb8x6b/pdb
• 分子名称: Transmembrane protein PVRIG, Nectin-2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: complex, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28771.39

構造登録者

Hu, S.T.,Han, P.,Wang, H.,Qi, J.X. (登録日: 2023-11-21, 公開日: 2024-04-24, 最終更新日: 2024-07-24)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)