Mechanical stress and anionic lipids synergistically stabilize an atypical structure of the angiotensin II type 1 receptor (AT1).

ABSTRACT: Environmental factors, including mechanical stress and surrounding lipids, can influence the response of GPCRs, such as the mechanosensitive angiotensin II type 1 receptor (AT1). To investigate the impact of these factors on AT1 activation, we developed a steered molecular dynamics simulations protocol based on quaternion formalism. In this protocol, a pulling force was applied to the N-terminus of transmembrane helix 6 (TM6) to induce the TM6 opening characteristic of activation. Subsequently, the simulations were continued without constraints to allow the receptor to relax around the novel TM6 conformation under different conditions. We analyzed the responses of AT1 to membrane stretching, modeled by applying surface tension, in different bilayers. In phosphocholine bilayers without surf

SUBMITTER: Ben Boubaker R 

PROVIDER: S-EPMC11560033 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature