Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation.
Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation.
Biochim Biophys Acta. 2011 Aug 8;
Authors: Mertz B, Struts AV, Feller SE, Brown MF
Abstract
Rhodopsin has served as the primary model for studying G protein-coupled receptors (GPCRs)-the largest group in the human genome, and consequently a primary target for pharmaceutical development. Understanding the functions and activation mechanisms of GPCRs has proven to be extraordinarily difficult, as they are part of a complex signaling cascade and reside within the cell membrane. Although X-ray crystallography has recently solved several GPCR structures that may resemble the activated conformation, the dynamics and mechanism of rhodopsin activation continue to remain elusive. Notably solid-state ((2))H NMR spectroscopy provides key information pertinent to how local dynamics of the retinal ligand change during rhodopsin activation. When combined with molecular mechanics simulations of proteolipid membranes, a new paradigm for the rhodopsin activation process emerges. Experiment and simulation both suggest that retinal isomerization initiates the rhodopsin photocascade to yield not a single activated structure, but rather an ensemble of activated conformational states. This article is part of a Special Issue entitled: Membrane protein structure and function.
PMID: 21851809 [PubMed - as supplied by publisher]
Source:
PubMed