Allosteric effects of sodium ion binding on activation of the m3 muscarinic g-protein-coupled receptor.

ABSTRACT: G-protein-coupled receptors (GPCRs) are important membrane proteins that mediate cellular signaling and represent primary targets for about one-third of currently marketed drugs. Recent x-ray crystallographic studies identified distinct conformations of GPCRs in the active and inactive states. An allosteric sodium ion was found bound to a highly conserved D2.50 residue in inactive GPCRs, whereas the D2.50 allosteric pocket became collapsed in active GPCR structures. However, the dynamic mechanisms underlying these observations remain elusive. In this study, we aimed to understand the mechanistic effects of sodium ion binding on dynamic activation of the M3 muscarinic GPCR through long-timescale accelerated molecular dynamics (aMD) simulations. Results showed that with the D2.50 residue dep

SUBMITTER: Miao Y 

PROVIDER: S-EPMC4390834 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature