Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor

• Published in: Science (American Association for the Advancement of Science) Vol. 289; no. 5480; pp. 739 - 745
• Main Authors: PALCZEWSKI, K, KUMASAKA, T, YAMAMOTO, M, MIYANO, M, HORI, T, BEHNKE, C. A, MOTOSHIMA, H, FOX, B. A, LE TRONG, I, TELLER, D. C, OKADA, T, STENKAMP, R. E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 04-08-2000; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: 11-cis-^ARetinal; Amino Acid Motifs; Amino Acid Sequence; Analysis; Animals; Biochemistry; Biological and medical sciences; Cattle; Cell Membrane - chemistry; Chromophores; Crystalline structure; Crystallography, X-Ray; Crystals; Datasets; Drug interactions; Fundamental and applied biological sciences. Psychology; Genetics; Heterotrimeric GTP-Binding Proteins - metabolism; Hydrogen Bonding; Light; Molecular biophysics; Molecular Sequence Data; Molecular structure; Molecules; Polar regions; Proteins; Receptors; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Research Article; Retinaldehyde - chemistry; Retinaldehyde - metabolism; Rhodopsin; Rhodopsin - chemistry; Rhodopsin - metabolism; Schiff Bases; Space life sciences; Stereoisomerism; Stimuli; Structural Elements (Construction); Structure in molecular biology; Ungulates; Vision, Ocular; Signal transduction; Rhodopsin; Molecular structure; Photoactivation; Molecular interaction; Helical structure; Crystallography; X ray diffraction; Chromophore; G protein; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.289.5480.739

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 α 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.