Sci Aug. 4, 2000
Biochemistry
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Krzysztof Palczewski,1,2,3* Takashi Kumasaka,7 Tetsuya Hori,7,8 Craig A.
Behnke,4,6 Hiroyuki Motoshima,7 Brian A. Fox,4,6 Isolde Le Trong,5,6 David C.
Teller,4,6 Tetsuji Okada,1 Ronald E. Stenkamp,5,6* Masaki Yamamoto,7 Masashi
Miyano7*
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors
(GPCRs) respond to a variety of different external stimuli and activate G
proteins. GPCRs share many structural features, including a bundle of seven
transmembrane helices connected by six loops of varying lengths. We determined
the structure of rhodopsin from diffraction data extending to 2.8 angstroms
resolution. The highly organized structure in the extracellular region,
including a conserved disulfide bridge, forms a basis for the arrangement of
the seven-helix transmembrane motif. The ground-state chromophore,
11-cis-retinal, holds the transmembrane region of the protein in the inactive
conformation. Interactions of the chromophore with a cluster of key residues
determine the wavelength of the maximum absorption. Changes in these
interactions among rhodopsins facilitate color discrimination. Identification
of a set of residues that mediate interactions between the transmembrane
helices and the cytoplasmic surface, where G-protein activation occurs, also
suggests a possible structural change upon photoactivation.
1 Department of Ophthalmology,
2 Department of Pharmacology,
3 Department of Chemistry,
4 Department of Biochemistry,
5 Department of Biological Structure, and
6 Biomolecular Structure Center, University of Washington, Seattle, WA
98195, USA.
7 Structural Biophysics Laboratory, RIKEN Harima Institute, 1-1-1 Kouto,
Mikazuki-cho, Sayo-gun, Hyogo 679-5148, Japan.
8 Graduate School of Bioscience and Biotechnology, Tokyo Institute of
Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan
* To whom correspondence should be addressed. E-mail: miyano at spring8.or.jp
(M.M.); palczews at u.washington.edu (K.P.); stenkamp at u.washington.edu (R.E.S.).
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