Mechanisms of peptide agonist dissociation and deactivation of adhesion G-protein-coupled receptors.

ABSTRACT: Adhesion G protein-coupled receptors (ADGRs) belong to Class B2 of GPCRs and are involved in a wide array of important physiological processes. ADGRs contain a GPCR autoproteolysis-inducing (GAIN) domain that is proximal to the receptor N-terminus and undergoes autoproteolysis during biosynthesis to generate two fragments: the N-terminal fragment (NTF) and C-terminal fragment (CTF). Dissociation of NTF reveals a tethered agonist to activate CTF of ADGRs for G protein signaling. Synthetic peptides that mimic the tethered agonist can also activate the ADGRs. However, mechanisms of peptide agonist dissociation and deactivation of ADGRs remain poorly understood. In this study, we have performed all-atom enhanced sampling simulations using a novel Protein-Protein Interaction-Gaussian accelerate

SUBMITTER: Joshi K 

PROVIDER: S-EPMC11419055 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature