Abstract
Rhodopsin is a key light-sensitive protein expressed exclusively in rod photoreceptor cells of the retina. Failure to express this transmembrane protein causes a lack of rod outer segment formation and progressive retinal degeneration, including the loss of cone photoreceptor cells. Molecular studies of rhodopsin have paved the way to understanding a large family of cell-surface membrane proteins called G protein-coupled receptors (GPCRs). Work started on rhodopsin over 100 years ago still continues today with substantial progress made every year. These activities underscore the importance of rhodopsin as a prototypical GPCR and receptor required for visual perception—the fundamental process of translating light energy into a biochemical cascade of events culminating in vision.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kuhne W (1977) Chemical processes in the retina. Vision Res 17:1269–1316
Salom D, Le Trong I, Pohl E et al (2006) Improvements in G protein-coupled receptor purification yield light stable rhodopsin crystals. J Struct Biol 156:497–504
Salom D, Lodowski DT, Stenkamp RE et al (2006) Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc Natl Acad Sci U S A 103:16123–16128
Kiser PD, Golczak M, Palczewski K (2014) Chemistry of the retinoid (visual) cycle. Chem Rev 114:194–232
Wald G (1968) Molecular basis of visual excitation. Science 162:230–239
Wald G (1935) Carotenoids and the visual cycle. J Gen Physiol 19:351–371
Hubbard R, Wald G (1952) Cis-trans isomers of vitamin A and retinene in the rhodopsin system. J Gen Physiol 36:269–315
Wald G, Brown PK (1953) The molar extinction of rhodopsin. J Gen Physiol 37:189–200
Matthews RG, Hubbard R, Brown PK et al (1963) Tautomeric forms of metarhodopsin. J Gen Physiol 47:215–240
Zhukovsky EA, Robinson PR, Oprian DD (1992) Changing the location of the Schiff base counterion in rhodopsin. Biochemistry 31:10400–10405
Zvyaga TA, Min KC, Beck M et al (1993) Movement of the retinylidene Schiff base counterion in rhodopsin by one helix turn reverses the pH dependence of the metarhodopsin I to metarhodopsin II transition. J Biol Chem 268:4661–4667
Palczewski K (2006) G protein-coupled receptor rhodopsin. Annu Rev Biochem 75:743–767
Palczewski K (2012) Chemistry and biology of vision. J Biol Chem 287:1612–1619
Mustafi D, Maeda T, Kohno H et al (2012) Inflammatory priming predisposes mice to age-related retinal degeneration. J Clin Invest 122:2989–3001
Jeon CJ, Strettoi E, Masland RH (1998) The major cell populations of the mouse retina. J Neurosci 18:8936–8946
Curcio CA, Sloan KR Jr, Packer O et al (1987) Distribution of cones in human and monkey retina: individual variability and radial asymmetry. Science 236:579–582
Nickell S, Park PS, Baumeister W et al (2007) Three-dimensional architecture of murine rod outer segments determined by cryoelectron tomography. J Cell Biol 177:917–925
Filipek S, Stenkamp RE, Teller DC et al (2003) G protein-coupled receptor rhodopsin: a prospectus. Annu Rev Physiol 65:851–879
Oprian DD, Molday RS, Kaufman RJ et al (1987) Expression of a synthetic bovine rhodopsin gene in monkey kidney cells. Proc Natl Acad Sci U S A 84:8874–8878
Hubbell WL, Altenbach C, Hubbell CM et al (2003) Rhodopsin structure, dynamics, and activation: a perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking. Adv Protein Chem 63:243–290
Grunbeck A, Huber T, Abrol R et al (2012) Genetically encoded photo-cross-linkers map the binding site of an allosteric drug on a G protein-coupled receptor. ACS Chem Biol 7:967–972
Daggett KA, Sakmar TP (2011) Site-specific in vitro and in vivo incorporation of molecular probes to study G-protein-coupled receptors. Curr Opin Chem Biol 15:392–398
Salom D, Cao P, Sun W et al (2012) Heterologous expression of functional G-protein-coupled receptors in Caenorhabditis elegans. FASEB J 26:492–502
Cao P, Sun W, Kramp K et al (2012) Light-sensitive coupling of rhodopsin and melanopsin to G(i/o) and G(q) signal transduction in Caenorhabditis elegans. FASEB J 26:480–491
Palczewski K, Kumasaka T, Hori T et al (2000) Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289:739–745
Teller DC, Okada T, Behnke CA et al (2001) Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). Biochemistry 40:7761–7772
Menon ST, Han M, Sakmar TP (2001) Rhodopsin: structural basis of molecular physiology. Physiol Rev 81:1659–1688
Smith SO (2010) Structure and activation of the visual pigment rhodopsin. Annu Rev Biophys 39:309–328
Park JH, Morizumi T, Li Y et al (2013) Opsin, a structural model for olfactory receptors? Angew Chem Int Ed Engl 52:11021–11024
Choe HW, Kim YJ, Park JH et al (2011) Crystal structure of metarhodopsin II. Nature 471:651–655
Scheerer P, Park JH, Hildebrand PW et al (2008) Crystal structure of opsin in its G-protein-interacting conformation. Nature 455:497–502
Park JH, Scheerer P, Hofmann KP et al (2008) Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454:183–187
Park JH, Krauss N, Pulvermuller A et al (2005) Crystallization and preliminary X-ray studies of mouse centrin1. Acta Crystallogr Sect F Struct Biol Cryst Commun 61:510–513
Singhal A, Ostermaier MK, Vishnivetskiy SA et al (2013) Insights into congenital stationary night blindness based on the structure of G90D rhodopsin. EMBO Rep 14:520–526
Deupi X, Edwards P, Singhal A et al (2012) Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II. Proc Natl Acad Sci U S A 109:119–124
Standfuss J, Xie G, Edwards PC et al (2007) Crystal structure of a thermally stable rhodopsin mutant. J Mol Biol 372:1179–1188
Li J, Edwards PC, Burghammer M et al (2004) Structure of bovine rhodopsin in a trigonal crystal form. J Mol Biol 343:1409–1438
Nakamichi H, Okada T (2007) X-ray crystallographic analysis of 9-cis-rhodopsin, a model analogue visual pigment. Photochem Photobiol 83:232–235
Schreiber M, Sugihara M, Okada T et al (2006) Quantum mechanical studies on the crystallographic model of bathorhodopsin. Angew Chem Int Ed Engl 45:4274–4277
Nakamichi H, Okada T (2006) Local peptide movement in the photoreaction intermediate of rhodopsin. Proc Natl Acad Sci U S A 103:12729–12734
Okada T, Sugihara M, Bondar AN et al (2004) The retinal conformation and its environment in rhodopsin in light of a new 2.2 A crystal structure. J Mol Biol 342:571–583
Nakamichi H, Buss V, Okada T (2007) Photoisomerization mechanism of rhodopsin and 9-cis-rhodopsin revealed by x-ray crystallography. Biophys J 92:L106–L108
Palczewski K, Orban T (2013) From atomic structures to neuronal functions of g protein-coupled receptors. Annu Rev Neurosci 36:139–164
Ovchinnikov YA (1987) Structure of rhodopsin and bacteriorhodopsin. Photochem Photobiol 45:909–914
Hargrave PA (2001) Rhodopsin structure, function, and topography the Friedenwald lecture. Invest Ophthalmol Vis Sci 42:3–9
Mirzadegan T, Benko G, Filipek S et al (2003) Sequence analyses of G-protein-coupled receptors: similarities to rhodopsin. Biochemistry 42:2759–2767
Applebury ML, Hargrave PA (1986) Molecular biology of the visual pigments. Vision Res 26:1881–1895
Karnik SS, Sakmar TP, Chen HB et al (1988) Cysteine residues 110 and 187 are essential for the formation of correct structure in bovine rhodopsin. Proc Natl Acad Sci U S A 85:8459–8463
Karnik SS, Khorana HG (1990) Assembly of functional rhodopsin requires a disulfide bond between cysteine residues 110 and 187. J Biol Chem 265:17520–17524
Papac DI, Thornburg KR, Bullesbach EE et al (1992) Palmitylation of a G-protein coupled receptor. Direct analysis by tandem mass spectrometry. J Biol Chem 267:16889–16894
Ovchinnikov YA, Abdulaev NG, Bogachuk AS (1988) Two adjacent cysteine residues in the C-terminal cytoplasmic fragment of bovine rhodopsin are palmitylated. FEBS Lett 230:1–5
Maeda A, Okano K, Park PS et al (2010) Palmitoylation stabilizes unliganded rod opsin. Proc Natl Acad Sci U S A 107:8428–8433
Kaushal S, Ridge KD, Khorana HG (1994) Structure and function in rhodopsin: the role of asparagine-linked glycosylation. Proc Natl Acad Sci U S A 91:4024–4028
Wheatley M, Wootten D, Conner MT et al (2012) Lifting the lid on GPCRs: the role of extracellular loops. Br J Pharmacol 165:1688–1703
Wheatley M, Hawtin SR (1999) Glycosylation of G-protein-coupled receptors for hormones central to normal reproductive functioning: its occurrence and role. Hum Reprod Update 5:356–364
Kranich H, Bartkowski S, Denton MJ et al (1993) Autosomal dominant ‘sector’ retinitis pigmentosa due to a point mutation predicting an Asn-15-Ser substitution of rhodopsin. Hum Mol Genet 2:813–814
Fukuda MN, Papermaster DS, Hargrave PA (1979) Rhodopsin carbohydrate. Structure of small oligosaccharides attached at two sites near the NH2 terminus. J Biol Chem 254:8201–8207
Salom D, Wang B, Dong Z et al (2012) Post-translational modifications of the serotonin type 4 receptor heterologously expressed in mouse rod cells. Biochemistry 51:214–224
Crouch RK (1986) Studies of rhodopsin and bacteriorhodopsin using modified retinals. Photochem Photobiol 44:803–807
Estevez ME, Kolesnikov AV, Ala-Laurila P et al (2009) The 9-methyl group of retinal is essential for rapid Meta II decay and phototransduction quenching in red cones. J Gen Physiol 134:137–150
Buczylko J, Saari JC, Crouch RK et al (1996) Mechanisms of opsin activation. J Biol Chem 271:20621–20630
Palczewski K (2010) Retinoids for treatment of retinal diseases. Trends Pharmacol Sci 31:284–295
Maeda T, Imanishi Y, Palczewski K (2003) Rhodopsin phosphorylation: 30 years later. Prog Retin Eye Res 22:417–434
Ohguro H, Palczewski K, Ericsson LH et al (1993) Sequential phosphorylation of rhodopsin at multiple sites. Biochemistry 32:5718–5724
Palczewski K, Buczylko J, Kaplan MW et al (1991) Mechanism of rhodopsin kinase activation. J Biol Chem 266:12949–12955
Kennedy MJ, Lee KA, Niemi GA et al (2001) Multiple phosphorylation of rhodopsin and the in vivo chemistry underlying rod photoreceptor dark adaptation. Neuron 31:87–101
Lee KA, Nawrot M, Garwin GG et al (2010) Relationships among visual cycle retinoids, rhodopsin phosphorylation, and phototransduction in mouse eyes during light and dark adaptation. Biochemistry 49:2454–2463
Struts AV, Salgado GF, Martinez-Mayorga K et al (2011) Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation. Nat Struct Mol Biol 18:392–394
Renthal R (2008) Buried water molecules in helical transmembrane proteins. Protein Sci 17:293–298
Buss V, Sugihara M, Entel P et al (2003) Thr94 and Wat2b effect protonation of the retinal chromophore in rhodopsin. Angew Chem Int Ed Engl 42:3245–3247
Jastrzebska B, Palczewski K, Golczak M (2011) Role of bulk water in hydrolysis of the rhodopsin chromophore. J Biol Chem 286:18930–18937
Padayatti PS, Wang L, Gupta S et al (2013) A hybrid structural approach to analyze ligand binding by the serotonin type 4 receptor (5-HT4). Mol Cell Proteomics 12:1259–1271
Angel TE, Gupta S, Jastrzebska B et al (2009) Structural waters define a functional channel mediating activation of the GPCR, rhodopsin. Proc Natl Acad Sci U S A 106:14367–14372
Hofmann KP, Scheerer P, Hildebrand PW et al (2009) A G protein-coupled receptor at work: the rhodopsin model. Trends Biochem Sci 34:540–552
Angel TE, Chance MR, Palczewski K (2009) Conserved waters mediate structural and functional activation of family A (rhodopsin-like) G protein-coupled receptors. Proc Natl Acad Sci U S A 106:8555–8560
Fritze O, Filipek S, Kuksa V et al (2003) Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation. Proc Natl Acad Sci U S A 100:2290–2295
Dryja TP, McGee TL, Reichel E et al (1990) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343:364–366
Nathans J (1992) Rhodopsin: structure, function, and genetics. Biochemistry 31:4923–4931
Malanson KM, Lem J (2009) Rhodopsin-mediated retinitis pigmentosa. Prog Mol Biol Transl Sci 88:1–31
Rosenfeld PJ, Cowley GS, McGee TL et al (1992) A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa. Nat Genet 1:209–213
Kumaramanickavel G, Maw M, Denton MJ et al (1994) Missense rhodopsin mutation in a family with recessive RP. Nat Genet 8:10–11
Hamel C (2006) Retinitis pigmentosa. Orphanet J Rare Dis 1:40
Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809
Jastrzebska B, Ringler P, Lodowski DT et al (2011) Rhodopsin-transducin heteropentamer: three-dimensional structure and biochemical characterization. J Struct Biol 176:387–394
Sekharan S, Morokuma K (2011) QM/MM study of the structure, energy storage, and origin of the bathochromic shift in vertebrate and invertebrate bathorhodopsins. J Am Chem Soc 133:4734–4737
Gonzalez-Luque R, Garavelli M, Bernardi F et al (2000) Computational evidence in favor of a two-state, two-mode model of the retinal chromophore photoisomerization. Proc Natl Acad Sci U S A 97:9379–9384
Mertz B, Struts AV, Feller SE et al (2012) Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation. Biochim Biophys Acta 1818:241–251
Liang Y, Fotiadis D, Maeda T et al (2004) Rhodopsin signaling and organization in heterozygote rhodopsin knockout mice. J Biol Chem 279:48189–48196
Fotiadis D, Liang Y, Filipek S et al (2003) Atomic-force microscopy: rhodopsin dimers in native disc membranes. Nature 421:127–128
Park PS, Filipek S, Wells JW et al (2004) Oligomerization of G protein-coupled receptors: past, present, and future. Biochemistry 43:15643–15656
Comar WD, Schubert SM, Jastrzebska B et al (2014) Time-resolved fluorescence spectroscopy measures clustering and mobility of a G protein-coupled receptor opsin in live cell membranes. J Am Chem Soc 136:8342–8349
Fotiadis D, Jastrzebska B, Philippsen A et al (2006) Structure of the rhodopsin dimer: a working model for G-protein-coupled receptors. Curr Opin Struct Biol 16:252–259
Jastrzebska B, Orban T, Golczak M et al (2013) Asymmetry of the rhodopsin dimer in complex with transducin. FASEB J 27:1572–1584
Sakami S, Maeda T, Bereta G et al (2011) Probing mechanisms of photoreceptor degeneration in a new mouse model of the common form of autosomal dominant retinitis pigmentosa due to P23H opsin mutations. J Biol Chem 286:10551–10567
Sakami S, Kolesnikov AV, Kefalov VJ et al (2013) P23H opsin knock-in mice reveal a novel step in retinal rod disc morphogenesis. Hum Mol Genet 23:1723–1741
Zhang N, Kolesnikov AV, Jastrzebska B et al (2013) Autosomal recessive retinitis pigmentosa E150K opsin mice exhibit photoreceptor disorganization. J Clin Invest 123:121–137
Acknowledgments
We thank Dr. Leslie T. Webster, Jr., and the members of Palczewski’s laboratory for their comments on the manuscript. The work was supported by funding from the National Eye Institute, National Institutes of Health Grants R01EY008061 (to K.P.). K.P. is the John H. Hord Professor of Pharmacology.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Hofmann, L., Palczewski, K. (2015). The G Protein-Coupled Receptor Rhodopsin: A Historical Perspective. In: Jastrzebska, B. (eds) Rhodopsin. Methods in Molecular Biology, vol 1271. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2330-4_1
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2330-4_1
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2329-8
Online ISBN: 978-1-4939-2330-4
eBook Packages: Springer Protocols