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Physiological Reviews, Vol. 81, No. 4, October 2001, pp. 1659-1688
Copyright ©2001 by the American Physiological Society
Howard Hughes Medical Institute, Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, New York, New York
Menon, Santosh T.,
May Han, and
Thomas P. Sakmar.
Rhodopsin: Structural Basis of Molecular Physiology. Physiol. Rev. 81: 1659-1688, 2001.
The crystal structure of rod cell visual pigment
rhodopsin was recently solved at 2.8-Å resolution. A critical
evaluation of a decade of structure-function studies is now
possible. It is also possible to begin to explain the structural basis
for several unique physiological properties of the vertebrate visual system, including extremely low dark noise levels as well as high gain
and color detection. The ligand-binding pocket of rhodopsin is
remarkably compact, and several apparent chromophore-protein interactions were not predicted from extensive mutagenesis or spectroscopic studies. The transmembrane helices are interrupted or
kinked at multiple sites. An extensive network of interhelical interactions stabilizes the ground state of the receptor. The helix
movement model of receptor activation, which might apply to all G
protein-coupled receptors (GPCRs) of the rhodopsin family, is
supported by several structural elements that suggest how
light-induced conformational changes in the ligand-binding
pocket are transmitted to the cytoplasmic surface. The cytoplasmic
domain of the receptor is remarkable for a carboxy-terminal helical
domain extending from the seventh transmembrane segment parallel to the
bilayer surface. Thus the cytoplasmic surface appears to be
approximately the right size to bind to the transducin heterotrimer in
a one-to-one complex. Future high-resolution structural studies of
rhodopsin and other GPCRs will form a basis to elucidate the detailed
molecular mechanism of GPCR-mediated signal transduction.
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