Transient ligand contacts of the intrinsically disordered N-terminus of neuropeptide Y₂ receptor regulate arrestin-3 recruitment.

ABSTRACT: Previous efforts in delineating molecular mechanisms of G protein-coupled receptor (GPCR) activation have focused on transmembrane regions and ligand-receptor contacts of the extracellular loops. The role of the highly flexible N-termini of rhodopsin-like GPCRs have not been well characterized to date. We hypothesize that transient contacts between the peptide ligand and the intrinsically disordered N-terminus (NT) of the neuropeptide Y (NPY) receptor Y₂ (Y₂R) will affect receptor signaling. We employ cross-linking mass spectrometry to capture ligand-receptor contacts including transient binding modes. A photo-reactive NPY analogue allows mapping the interaction between NPY and Y₂R NT resulting in a total number of 40 cross-links. The cross-links provide di

SUBMITTER: Kaiser A 

PROVIDER: S-EPMC12449476 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature