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Biochim Biophys Acta. 2012 Feb;1818(2):241-51. doi: 10.1016/j.bbamem.2011.08.003. Epub 2011 Aug 8.

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

Author information

1
Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.

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
PMCID:
PMC5270601
DOI:
10.1016/j.bbamem.2011.08.003
[Indexed for MEDLINE]
Free PMC Article

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