Deconstructing activation events in rhodopsin.

ABSTRACT: Activation of class-A G-protein-coupled receptors (GPCRs) involves large-scale reorganization of the H3/H6 interhelical network. In rhodopsin (Rh), this process is coupled to a change in the protonation state of a key residue, E134, whose exact role in activation is not well understood. Capturing this millisecond pH-dependent process is a well-appreciated challenge. We have developed a scheme combining the harmonic Fourier beads (HFB) method and constant-pH molecular dynamics with pH-based replica exchange (pH-REX) to gain insight into the structural changes that occur along the activation pathway as a function of the protonation state of E134. Our results indicate that E134 is protonated as a consequence of tilting of H6 by ca. 4.0° with respect to its initial position and simultaneous ro

SUBMITTER: Laricheva EN 

PROVIDER: S-EPMC3774788 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature