Delineating the conformational landscape and intrinsic properties of the angiotensin II type 2 receptor using a computational study.

ABSTRACT: As a key regulator for the renin-angiotensin system, a class A G protein-coupled receptor (GPCR), AngII type 2 receptor (AT₂R), plays a pivotal role in the homeostasis of the cardiovascular system. Compared with other GPCRs, AT₂R has a unique antagonist-bound conformation and its mechanism is still an enigma. Here, we applied combined dynamic and evolutional approaches to investigate the conformational space and intrinsic properties of AT₂R. With molecular dynamic simulations, Markov State Models, and statistics coupled analysis, we captured the conformational landscape of AT₂R and identified its uniquity from both dynamical and evolutional viewpoints. A cryptic pocket was also discovered in the intermediate state during conformation transitions.

SUBMITTER: Cong X 

PROVIDER: S-EPMC9117689 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature