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PMID: 21851809 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Review

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

Biochimica et biophysica acta ·Vol. 1818 ·No. 2 ·2012-02-00 ·Pages 241-51

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.

MeSH Terms
Cell Membrane/chemistry,metabolism Humans Magnetic Resonance Spectroscopy Molecular Dynamics Simulation Protein Conformation Rhodopsin/chemistry,metabolism
Chemicals
Rhodopsin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mertz Blake
Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
Struts Andrey V
Feller Scott E
Brown Michael F
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Article Info
Journal
Biochimica et biophysica acta
Abbr.
Biochim Biophys Acta
ISSN
0006-3002
DOI
10.1016/j.bbamem.2011.08.003
Published
2012-02-00
Epub
2011-00-08
Pages
241-51
Language
English
Region
Netherlands
NLM ID
0217513
PMCID
PMC5270601
Subset
IM
Grants
NEI NIH HHS · EY019614 · United States
NEI NIH HHS · R01 EY018891 · United States
NEI NIH HHS · R01 EY012049 · United States
NEI NIH HHS · EY012049 · United States
NEI NIH HHS · EY018891 · United States
External Links
PubMed source DOI: 10.1016/j.bbamem.2011.08.003 PMC Full Text
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