Conformational dynamics of the active state of β-arrestin 1.

ABSTRACT: β-arrestins (βarr) regulate the signaling and trafficking of G protein-coupled receptors (GPCRs) in numerous physiological processes and have been implicated in various diseases. Structural and kinetic insights into how ligand-mediated GPCR activation drives βarr coupling and activation remain limited, with the binding mechanism of the phosphorylated GPCR C-terminal tails, such as that of the vasopressin receptor-2 (V2Rpp), and the conformation of the entire βarr tail in the active state still unknown. Here, we simulated both the basal and V2Rpp-bound states of βarr1 with temperature replica-exchange molecular dynamics (TREMD) simulations to probe the activation mechanism of βarr1. Compared to conventional MD, our TREMD simulations, employing an unprecedented 200-replica setup, significant

SUBMITTER: Ngo V 

PROVIDER: S-EPMC12259068 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature