Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation

Blake Mertz, Andrey V. Struts, Scott E. Feller, Michael F. Brown

Research output: Contribution to journalReview article

26 Scopus citations

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 2H 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.

Original languageEnglish (US)
Pages (from-to)241-251
Number of pages11
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1818
Issue number2
DOIs
StatePublished - Feb 1 2012

Keywords

  • G protein-coupled receptor
  • Membrane
  • Molecular dynamics
  • Rhodopsin
  • Solid-state NMR
  • Vision

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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