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Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Krzysztof Palczewski,123*Takashi Kumasaka,7Tetsuya Hori,78Craig A. Behnke,46Hiroyuki Motoshima,7Brian A. Fox,46Isolde Le Trong,56David C. Teller,46Tetsuji Okada,1Ronald E. Stenkamp,56*Masaki Yamamoto,7Masashi Miyano7*
Heterotrimeric guanine nucleotide-binding protein (G
protein)-coupled receptors (GPCRs) respond to a variety of
differentexternal stimuli and activate G proteins. GPCRs share many
structuralfeatures, including a bundle of seven transmembrane helicesconnected by six loops of varying lengths. We determined the
structureof rhodopsin from diffraction data extending to 2.8 angstromsresolution. The highly organized structure in the extracellularregion,
including a conserved disulfide bridge, forms a basisfor the
arrangement of the seven-helix transmembrane motif. Theground-state
chromophore, 11-cis-retinal, holds the transmembraneregion
of the protein in the inactive conformation. Interactionsof the
chromophore with a cluster of key residues determine thewavelength of
the maximum absorption. Changes in these interactionsamong rhodopsins
facilitate color discrimination. Identificationof a set of residues
that mediate interactions between the transmembranehelices and the
cytoplasmic surface, where G-protein activationoccurs, 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.).
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Henry R. Bourne and Elaine C. Meng (4 August 2000) Science289 (5480), 733.
[DOI: 10.1126/science.289.5480.733] |Summary »|Full Text »
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318, 1258-1265
|Abstract »|Full Text »|PDF »
Isolation and characterization of melanopsin (Opn4) from the Australian marsupial Sminthopsis crassicaudata (fat-tailed dunnart).
S. S Pires, J. Shand, J. Bellingham, C. Arrese, M. Turton, S. Peirson, R. G Foster, and S. Halford (2007)
Proc R Soc B
274, 2791-2799
|Abstract »|Full Text »|PDF »
Functional Analysis of Transmembrane Domain 2 of the M1 Muscarinic Acetylcholine Receptor.
Inhibitory role of CXCR4 glycan in CD4-independent X4-tropic human immunodeficiency virus type 1 infection and its abrogation in CD4-dependent infection.
Y. Kubo, M. Yokoyama, H. Yoshii, C. Mitani, C. Tominaga, Y. Tanaka, H. Sato, and N. Yamamoto (2007)
J. Gen. Virol.
88, 3139-3144
|Abstract »|Full Text »|PDF »
Assessment of the Roles of Serines 5.43(239) and 5.46(242) for Binding and Potency of Agonist Ligands at the Human Serotonin 5-HT2A Receptor.
Transmembrane Segment IV Contributes a Functionally Important Interface for Oligomerization of the Class II G Protein-coupled Secretin Receptor.
K. G. Harikumar, D. I. Pinon, and L. J. Miller (2007)
J. Biol. Chem.
282, 30363-30372
|Abstract »|Full Text »|PDF »
Identification of Residues Important for Agonist Recognition and Activation in GPR40.
C. S. Sum, I. G. Tikhonova, S. Neumann, S. Engel, B. M. Raaka, S. Costanzi, and M. C. Gershengorn (2007)
J. Biol. Chem.
282, 29248-29255
|Abstract »|Full Text »|PDF »
Pituitary-Thyroid Setpoint and Thyrotropin Receptor Expression in Consomic Rats.
L. C. Moeller, M. Alonso, X. Liao, V. Broach, A. Dumitrescu, J. Van Sande, L. Montanelli, S. Skjei, C. Goodwin, H. Grasberger, et al. (2007)
Endocrinology
148, 4727-4733
|Abstract »|Full Text »|PDF »
Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4.
C.-c. Huang, S. N. Lam, P. Acharya, M. Tang, S.-H. Xiang, S. S.-u. Hussan, R. L. Stanfield, J. Robinson, J. Sodroski, I. A. Wilson, et al. (2007)
Science
317, 1930-1934
|Abstract »|Full Text »|PDF »
Mechanism of Activation of a G Protein-coupled Receptor, the Human Cholecystokinin-2 Receptor.
E. Marco, M. Foucaud, I. Langer, C. Escrieut, I. G. Tikhonova, and D. Fourmy (2007)
J. Biol. Chem.
282, 28779-28790
|Abstract »|Full Text »|PDF »
Small Molecule Receptor Agonists and Antagonists of CCR3 Provide Insight into Mechanisms of Chemokine Receptor Activation.
E. L. Wise, C. Duchesnes, P. C. A. da Fonseca, R. A. Allen, T. J. Williams, and J. E. Pease (2007)
J. Biol. Chem.
282, 27935-27943
|Abstract »|Full Text »|PDF »
Distinct Structural Changes in a G Protein-coupled Receptor Caused by Different Classes of Agonist Ligands.
J. H. Li, S.-J. Han, F. F. Hamdan, S.-K. Kim, K. A. Jacobson, L. M. Bloodworth, X. Zhang, and J. Wess (2007)
J. Biol. Chem.
282, 26284-26293
|Abstract »|Full Text »|PDF »
Functional characterization, tuning, and regulation of visual pigment gene expression in an anadromous lamprey.
W. L. Davies, J. A. Cowing, L. S. Carvalho, I. C. Potter, A. E. O. Trezise, D. M. Hunt, and S. P. Collin (2007)
FASEB J
21, 2713-2724
|Abstract »|Full Text »|PDF »
Gene Duplication Is an Evolutionary Mechanism for Expanding Spectral Diversity in the Long-Wavelength Photopigments of Butterflies.
F. D. Frentiu, G. D. Bernard, M. P. Sison-Mangus, A. Van Zandt Brower, and A. D. Briscoe (2007)
Mol. Biol. Evol.
24, 2016-2028
|Abstract »|Full Text »|PDF »
Critical Role for the Second Extracellular Loop in the Binding of Both Orthosteric and Allosteric G Protein-coupled Receptor Ligands.
V. A. Avlani, K. J. Gregory, C. J. Morton, M. W. Parker, P. M. Sexton, and A. Christopoulos (2007)
J. Biol. Chem.
282, 25677-25686
|Abstract »|Full Text »|PDF »
Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor.
C. Parthier, M. Kleinschmidt, P. Neumann, R. Rudolph, S. Manhart, D. Schlenzig, J. Fanghanel, J.-U. Rahfeld, H.-U. Demuth, and M. T. Stubbs (2007)
PNAS
104, 13942-13947
|Abstract »|Full Text »|PDF »
Helix 8 Leu in the CB1 Cannabinoid Receptor Contributes to Selective Signal Transduction Mechanisms.
S. Anavi-Goffer, D. Fleischer, D. P. Hurst, D. L. Lynch, J. Barnett-Norris, S. Shi, D. L. Lewis, S. Mukhopadhyay, A. C. Howlett, P. H. Reggio, et al. (2007)
J. Biol. Chem.
282, 25100-25113
|Abstract »|Full Text »|PDF »
Trapping of a Nonpeptide Ligand by the Extracellular Domains of the Gonadotropin-Releasing Hormone Receptor Results in Insurmountable Antagonism.
T. A. Kohout, Q. Xie, S. Reijmers, K. J. Finn, Z. Guo, Y.-F. Zhu, and R. S. Struthers (2007)
Mol. Pharmacol.
72, 238-247
|Abstract »|Full Text »|PDF »
Receptor-Mediated Activation of Heterotrimeric G-Proteins: Current Structural Insights.
Molecular Approximations between Residues 21 and 23 of Secretin and Its Receptor: Development of a Model for Peptide Docking with the Amino Terminus of the Secretin Receptor.
M. Dong, P. C.-H. Lam, F. Gao, K. Hosohata, D. I. Pinon, P. M. Sexton, R. Abagyan, and L. J. Miller (2007)
Mol. Pharmacol.
72, 280-290
|Abstract »|Full Text »|PDF »
Molecular Interaction of a Potent Nonpeptide Agonist with the Chemokine Receptor CCR8.
P. C. Jensen, R. Nygaard, S. Thiele, A. Elder, G. Zhu, R. Kolbeck, S. Ghosh, T. W. Schwartz, and M. M. Rosenkilde (2007)
Mol. Pharmacol.
72, 327-340
|Abstract »|Full Text »|PDF »
Statistical prediction of protein chemical interactions based on chemical structure and mass spectrometry data.
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.
