Biased agonists differentially modulate the receptor conformation ensembles in Angiotensin II type 1 receptor.

ABSTRACT: The structural features that contribute to the efficacy of biased agonists targeting G protein-coupled receptors (GPCRs) towards G proteins or β-arrestin (β-arr) signaling pathways is nebulous, although such knowledge is critical in designing biased ligands. The dynamics of the agonist-GPCR complex is one of the critical factors in determining agonist bias. Angiotensin II type I receptor (AT1R) is an ideal model system to study the molecular basis of bias since it has multiple β-arr2 and Gq protein biased agonists as well as experimentally solved three dimensional structures. Using Molecular Dynamics (MD) simulations for the Angiotensin II type I receptor (AT1R) bound to ten different agonists, we infer that the agonist bound receptor samples conformations with different relative weights,

SUBMITTER: Nivedha AK 

PROVIDER: S-EPMC9769363 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature