Molecular insights into ligand recognition and receptor activation of GPR15.

ABSTRACT: In response to the chemokine-like peptide GPR15L, G protein-coupled receptor 15 (GPR15) is crucial for immune cell trafficking and inflammatory diseases. However, understanding of its physiology and pathology is hindered by lack of molecular details of the interaction between GPR15 and the full-length GPR15L. Here, we report the structure of GPR15 bound to the full-length GPR15L and G_i3 protein. Combined with mutagenesis data, this structure reveals key interactions that define ligand recognition and a subpocket that governs GPR15L selectivity and receptor activation. Molecular dynamics simulations suggest that sulfation modifications in the N-terminal region of GPR15 may play a role in stabilizing the binding between GPR15 and the core region of GPR15L. Furthermore, molecular d

SUBMITTER: Chen S 

PROVIDER: S-EPMC12663730 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature