title: Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Blake
authors.initials: B
authors.lastname: Mertz
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Struts
authors.forename: Scott E
authors.initials: SE
authors.lastname: Feller
authors.forename: Michael F
authors.initials: MF
authors.lastname: Brown
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012243:Rhodopsin