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 journalArticle

26 Citations (Scopus)

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
JournalBBA - Biomembranes
Volume1818
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Rhodopsin
Chemical activation
Nuclear magnetic resonance
G-Protein-Coupled Receptors
Proteolipids
Molecular mechanics
X ray crystallography
X Ray Crystallography
Human Genome
Cell membranes
Isomerization
Mechanics
Nuclear magnetic resonance spectroscopy
Conformations
Membrane Proteins
Magnetic Resonance Spectroscopy
Genes
Cell Membrane
Ligands
Membranes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

Cite this

Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation. / Mertz, Blake; Struts, Andrey V.; Feller, Scott E.; Brown, Michael F.

In: BBA - Biomembranes, Vol. 1818, No. 2, 02.2012, p. 241-251.

Research output: Contribution to journalArticle

Mertz, Blake ; Struts, Andrey V. ; Feller, Scott E. ; Brown, Michael F. / Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation. In: BBA - Biomembranes. 2012 ; Vol. 1818, No. 2. pp. 241-251.
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