Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1818, Issue 2, Pages 241-251Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2011.08.003
Keywords
G protein-coupled receptor; Membrane; Molecular dynamics; Solid-state NMR; Rhodopsin; Vision
Categories
Funding
- U. S. National Institutes of Health [EY019614, EY012049, EY018891]
- U. S. National Science Foundation [MCB0950258]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [0950258] Funding Source: National Science Foundation
Ask authors/readers for more resources
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 H-2 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. (C) 2011 Published by Elsevier B.V.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available