Structural basis for the immune recognition and selectivity of the immune receptor PVRIG for ligand Nectin-2.
Structure
; 32(7): 918-929.e4, 2024 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-38626767
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.
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Base de dados:
MEDLINE
Assunto principal:
Ligação Proteica
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Modelos Moleculares
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Receptores de Superfície Celular
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Nectinas
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article