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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.).
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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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Dimerization and oligomerization of G-protein-coupled receptors: debated structures with established and emerging functions.
An Intracellular Allosteric Site for a Specific Class of Antagonists of the CC Chemokine G Protein-Coupled Receptors CCR4 and CCR5.
G. Andrews, C. Jones, and K. A. Wreggett (2008)
Mol. Pharmacol.
73, 855-867
|Abstract »|Full Text »|PDF »
Rhodopsin and 9-Demethyl-retinal Analog: EFFECT OF A PARTIAL AGONIST ON DISPLACEMENT OF TRANSMEMBRANE HELIX 6 IN CLASS A G PROTEIN-COUPLED RECEPTORS.
B. Knierim, K. P. Hofmann, W. Gartner, W. L. Hubbell, and O. P. Ernst (2008)
J. Biol. Chem.
283, 4967-4974
|Abstract »|Full Text »|PDF »
Efficient Coupling of Transducin to Monomeric Rhodopsin in a Phospholipid Bilayer.
M. R. Whorton, B. Jastrzebska, P. S.-H. Park, D. Fotiadis, A. Engel, K. Palczewski, and R. K. Sunahara (2008)
J. Biol. Chem.
283, 4387-4394
|Abstract »|Full Text »|PDF »
Characterization of G-Protein Coupled Receptor Kinase Interaction with the Neurokinin-1 Receptor Using Bioluminescence Resonance Energy Transfer.
R. Jorgensen, N. D. Holliday, J. L. Hansen, M. Vrecl, A. Heding, T. W. Schwartz, and C. E. Elling (2008)
Mol. Pharmacol.
73, 349-358
|Abstract »|Full Text »|PDF »
[3H]Org 43553, the First Low-Molecular-Weight Agonistic and Allosteric Radioligand for the Human Luteinizing Hormone Receptor.
L. H. Heitman, J. Oosterom, K. M. Bonger, C. M. Timmers, P. H. G. Wiegerinck, and A. P. IJzerman (2008)
Mol. Pharmacol.
73, 518-524
|Abstract »|Full Text »|PDF »
Conformational thermostabilization of the {beta}1-adrenergic receptor in a detergent-resistant form.
M. J. Serrano-Vega, F. Magnani, Y. Shibata, and C. G. Tate (2008)
PNAS
105, 877-882
|Abstract »|Full Text »|PDF »
Site-specific Incorporation of Keto Amino Acids into Functional G Protein-coupled Receptors Using Unnatural Amino Acid Mutagenesis.
S. Ye, C. Kohrer, T. Huber, M. Kazmi, P. Sachdev, E. C.Y. Yan, A. Bhagat, U. L. RajBhandary, and T. P. Sakmar (2008)
J. Biol. Chem.
283, 1525-1533
|Abstract »|Full Text »|PDF »
Expression of a Functional G Protein-Coupled Receptor 54-Kisspeptin Autoregulatory System in Hypothalamic Gonadotropin-Releasing Hormone Neurons.
S. Quaynor, L. Hu, P. K. Leung, H. Feng, N. Mores, L. Z. Krsmanovic, and K. J. Catt (2007)
Mol. Endocrinol.
21, 3062-3070
|Abstract »|Full Text »|PDF »
Roof and Floor of the Muscarinic Binding Pocket: Variations in the Binding Modes of Orthosteric Ligands.
J. A. Goodwin, E. C. Hulme, C. J. Langmead, and B. G. Tehan (2007)
Mol. Pharmacol.
72, 1484-1496
|Abstract »|Full Text »|PDF »
High-Resolution Crystal Structure of an Engineered Human 2-Adrenergic G Protein Coupled Receptor.
V. Cherezov, D. M. Rosenbaum, M. A. Hanson, S. G. F. Rasmussen, F. S. Thian, T. S. Kobilka, H.-J. Choi, P. Kuhn, W. I. Weis, B. K. Kobilka, et al. (2007)
Science
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.
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.
