Structural heterogeneity of the μ-opioid receptor's conformational ensemble in the apo state.

ABSTRACT: G-protein coupled receptors (GPCRs) are the largest and most pharmaceutically relevant family of membrane proteins. Here, fully unbiased, enhanced sampling simulations of a constitutively active mutant (CAM) of a class A GPCR, the μ-opioid receptor (μOR), demonstrates repeated transitions between the inactive (IS) and active-like (AS-L) states. The interconversion features typical activation/inactivation patterns involving established conformational rearrangements of conserved residues. By contrast, wild-type μOR remains in IS during the same course of simulation, consistent with the low basal activity of the protein. The simulations point to an important role of residue W293^6.48 at the "toggle switch" in the mutation-induced constitutive activation. Such role has been already o

SUBMITTER: Sena DM 

PROVIDER: S-EPMC5377942 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature