Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation. / Mertz, Blake; Struts, Andrey V.; Feller, Scott E.; Brown, Michael F.
In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1818, No. 2, 02.2012, p. 241-251.Research output: Contribution to journal › Review article › peer-review
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TY - JOUR
T1 - Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation
AU - Mertz, Blake
AU - Struts, Andrey V.
AU - Feller, Scott E.
AU - Brown, Michael F.
N1 - Funding Information: Research support from the U. S. National Institutes of Health ( EY019614 to BM and EY012049 and EY018891 to MFB) and the U. S. National Science Foundation ( MCB0950258 to SEF) is gratefully acknowledged. Copyright: Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - G protein-coupled receptor
KW - Membrane
KW - Molecular dynamics
KW - Rhodopsin
KW - Solid-state NMR
KW - Vision
UR - http://www.scopus.com/inward/record.url?scp=84855464554&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2011.08.003
DO - 10.1016/j.bbamem.2011.08.003
M3 - Review article
C2 - 21851809
VL - 1818
SP - 241
EP - 251
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
SN - 0005-2736
IS - 2
ER -
ID: 5520781