Skip to main content

Rhodopsin/G-Protein Interaction

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 108 / 2))

Abstract

Rhodopsin, the visual pigment of the rod cell, governs early steps of the visual process by its concerted interactions with the G-protein transducin, rhodopsin kinase, and arrestin. The precise interaction with transducin is crucial for single photon detection by rod cells. The rate of transducin turnover catalyzed by a single rhodopsin molecule in the dark is lower than 10−6 per second and increases to 103 after light activation. The visual receptor/G-protein system, designed for low noise-signal amplification, may operate near to the upper physical limit set to biological signal transduction. On the other hand, rhodopsin and transducin are fundamentally similar to other receptors and G-proteins, and understanding this specialized system may help to understand such systems in general. Studies of the visual system are supported by specific physical properties, as the activation by light, the colored receptor intermediates, and the variable membrane binding of the G-protein. Part of this chapter is dedicated to techniques of physical biochemistry and how to employ them in the study of rhodopsin/G-protein interaction. Some of the insights may also apply to the related systems. Other recent reviews deal with rhodopsin and transducin from different perspectives, including the role of rod outer segment structure (Liebman et al. 1987), molecular details of the interaction (Hamm 1991), structure and function of rhodopsin (Hargrave and McDowell 1992; Hargrave et al. 1993) and of seven-helix receptors in general (Hargrave 1991), molecular biology (Khorana 1992) and spectroscopy (Siebert 1992) of rhodopsin, and the role of transducin in the visual process (Hofmann and Kahlert 1992; Lamb and Pugh 1992).

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Applebury ML, Hargrave PA (1986) Molecular biology of the visual pigments. Vision Res 26:1881–1885.

    Article  PubMed  CAS  Google Scholar 

  • Bennett N, Michel-Villaz M, Kühn H (1982) Light-induced interaction between rhodopsin and the GTP-binding protein — metarhodopsin II is the major photoproduct involved. Eur J Biochem 127:97–103.

    Article  PubMed  CAS  Google Scholar 

  • Bennett N, Dupont Y (1985) The G-protein of retinal rod outer segments (transducin) — mechanism of interaction with rhodopsin and nucleotides. J Biol Chem 260:4156–4168.

    PubMed  CAS  Google Scholar 

  • Bignetti E, Cavaggioni A, Fasella P, Ottonello S, Rossi GL (1980) Light and GTP effects on the turbidity of frog visual membrane suspensions. Mol Cell Biochem 30:93–99.

    Article  PubMed  CAS  Google Scholar 

  • Bornancin F, Pfister C, Chabre M (1989) The transitory complex between photoexcited rhodopsin and transducin — reciprocal interaction between the retinal site in rhodopsin and the nucleotide site in transducin. Eur J Biochem 184:687–698.

    Article  PubMed  CAS  Google Scholar 

  • Bourne HR, Masters SB, Miller RT, Sullivan KA, Heidemann W (1988) Mutations probe structure and function of G-protein α chains. Cold Spring Harbor Symp Quant Biol LIII:221–228.

    Google Scholar 

  • Bruckert F, Vuong TM, Chabre M (1988) Light and GTP dependence of transducin solubility in retinal rods. Eur Biophys J 16:207–218.

    Article  PubMed  CAS  Google Scholar 

  • Buzdygon BE, Liebman PA (1984) Albumin inhibits light activation of cGMP phosphodiesterase on rod disc membranes. J Biol Chem 259:14567–14571.

    PubMed  CAS  Google Scholar 

  • Chabre M, Breton J (1979) The orientation of the chromophore of vertebrate rhodopsin in the “meta” intermediate states and the reversibility of the Meta II-Meta III transition. Vision Res 19:1005–1018.

    Article  PubMed  CAS  Google Scholar 

  • DeGrip (1988) Recent chemical studies related to vision. Photochem Photobiol 48:799–810.

    Article  PubMed  CAS  Google Scholar 

  • Dencher NA, Heberle J, Bark C, Koch MHJ, Rapp G, Oesterhelt D, Bartels K, Büldt G (1991) Proton translocation and conformational changes during the bacteriorhodopsin photocycle: time-resolved studies with membrane-bound optical probes and X-ray diffraction. Photochem Photobiol 54:881–887.

    Article  CAS  Google Scholar 

  • Dratz EA, Hargrave PA (1983) The structure of rhodopsin and the rod outer segment disc membrane. Trends Biochem Sci 8:128–131.

    Article  CAS  Google Scholar 

  • Emeis D, Hofmann KP (1981) Shift in the relation between flash-induced metarhodopsin I and metarhodopsin II within the first 10% rhodopsin bleaching in bovine disc membranes. FEBS Lett 136:201–207.

    Article  PubMed  CAS  Google Scholar 

  • Emeis D, Kühn H, Reichert J, Hofmann KP (1982) Complex formation between metarhodopsin II and GTP-binding protein in bovine photoreceptor membranes leads to a shift of the photoproduct equilibrium. FEBS Lett 143:29–34.

    Article  PubMed  CAS  Google Scholar 

  • Ferretti L, Karnik SS, Khorana HG, Nassal M, Oprian DD (1986) Total synthesis of a gene for bovine rhodopsin. Proc Natl Acad Sci USA 83:599–603.

    Article  PubMed  CAS  Google Scholar 

  • Franke RR, König B, Sakmar TP, Khorana HG, Hofmann KP (1990) Rhodopsin mutants that bind but fail to activate transducin. Science 250:123–125.

    Article  PubMed  CAS  Google Scholar 

  • Ganter UM, Schmid ED, Perez-Sala D, Rando RR, Siebert F (1989) Removal of the 9-methyl group of retinal inhibits signal transduction in the visual process — a Fourier transform infrared and biochemical investigation. Biochemistry 28:5954–5962.

    Article  PubMed  CAS  Google Scholar 

  • Ganter UM, Longstaff C, Pajares MA, Rando RR, Siebert F (1991) Fourier-transform Infrared studies of active-site methylated rhodopsin — implications for chromophore-protein interaction, transducin activation, and the reaction pathway. Biophys J 59:640–644.

    Article  PubMed  CAS  Google Scholar 

  • Ganter UM, Charitopoulos T, Virmaux N, Siebert F (to be published) Conformational changes of cytosolic loops of bovine rhodopsin during the transition to metarhodopsin. II. An investigation by Fourier transform infrared difference spectroscopy. Photochem Photobiol.

    Google Scholar 

  • Guy PM, Koland JG, Cerione RA (1990) Rhodopsin-stimulated activation-deactivation cycle of transducin: kinetics of the intrinsic fluorescence response of the α-subunit. Biochemistry 29:6954–6964.

    Article  PubMed  CAS  Google Scholar 

  • Hamm HE (1991) Molecular interactions between the photoreceptor G protein and rhodopsin. Cell Mol Neurobiol 11:563–578.

    Article  PubMed  CAS  Google Scholar 

  • Hamm HE, Deretic D, Hofmann KP, Schleicher A, Kohl B (1987) Mechanism of action of monoclonal antibodies that block the light-activation of the guanyl nucleotide binding protein, transducin. J Biol Chem 262:10831–10838.

    PubMed  CAS  Google Scholar 

  • Hamm HE, Deretic D, Arendt A, Hargrave PA, König B, Hofmann KP (1988) Site of G protein binding to rhodopsin mapped with synthetic peptides from the α subunit. Science 241:832–835.

    Article  PubMed  CAS  Google Scholar 

  • Hargrave PA (1991) Seven-helix receptors. Curr Opinion Struct Biol 1:575–581.

    Article  CAS  Google Scholar 

  • Hargrave PA, McDowell JM (to be published) Rhodopsin and phototransduction: a model system for G-protein linked receptors. FASEB J.

    Google Scholar 

  • Hargrave PA, Hamm HE, Hofmann KP (1993) Interaction of rhodopsin with the G-protein, transducin. Bioessays 15:43–50.

    Article  PubMed  CAS  Google Scholar 

  • Henderson R, Unwin PNT (1975) Three-dimensional model of purple membrane obtained by electron microscopy. Nature 257:28–32.

    Article  PubMed  CAS  Google Scholar 

  • Higashijima T, Ferguson KM, Sternweis PC, Ross EM, Smigel MD, Gilman AG (1987) The effect of activating ligands on the intrinsic fluorescence of guanine nuleotide-binding regulatory proteins. J Biol Chem 262:752–756.

    PubMed  CAS  Google Scholar 

  • Hofmann KP, Uhl R, Hoffmann W, Kreutz W (1976) Measurements of fast light-induced light-scattering and absorption changes in outer segments of vertebrate light sensitive rod cells. Biophys Struct Mech 2:61–77.

    Article  PubMed  CAS  Google Scholar 

  • Hofmann KP, Emeis D (1979) Differential light detector. Rev Sci Instr 50:249–252.

    Article  CAS  Google Scholar 

  • Hofmann KP, Emeis D (1981) Comparative kinetic light-scattering and-absorption photometry. Biophys Struct Mech 8:23–34.

    Article  CAS  Google Scholar 

  • Hofmann KP, Emeis D, Schnetkamp PPM (1983) Interplay between hydroxylamine, metarhodopsin II and GTP-binding protein in bovine photoreceptor-membranes. Biochim Biophys Acta 725:60–70.

    Article  PubMed  CAS  Google Scholar 

  • Hofmann KP (1984) Light-scattering signal of G-binding in rod outer segments depends on osmolarity. Invest Ophthal Vis Sci 25a:56.

    Google Scholar 

  • Hofmann KP (1985) Effect of GTP on the rhodopsin G-protein complex by transient formation of extra metarhodopsin II. Biochim Biophys Acata 810:278–281.

    Article  CAS  Google Scholar 

  • Hofmann KP, Reichert J (1985) Chemical probing of the light-induced interaction between rhodopsin and G-protein — near infrared light scattering and sulfhydryl modifications. J Biol Chem 260:7990–7995.

    PubMed  CAS  Google Scholar 

  • Hofmann KP (1986) Photoproducts of rhodopsin in the disc membrane. Photobiochem Photobiophys 13:309–338.

    CAS  Google Scholar 

  • Hofmann KP, Kahlert M (1992) The activation of transducin: studies on its mechanism and modulation. In: Hargrave PA, Hofmann KP, Kaupp UB (eds) Signal transduction in photoreceptor cells. Springer, Heidelberg, New York.

    Google Scholar 

  • Hofmann KP, Pulvermüller A, Buczylko J, Hooser PV, Palczewski K (1992) The role of arrestin and retinoids in the regeneration pathway of rhodopsin. J Biol Chem 267:15701–15706.

    PubMed  CAS  Google Scholar 

  • Kahlert M, König B, Hofmann KP (1990a) Displacement of rhodopsin by GDP from three-loop interaction with transducin depends critically on the diphosphate β-position. J Biol Chem 265:18928–18932.

    PubMed  CAS  Google Scholar 

  • Kahlert M, Pepperberg DR, Hofmann KP (1990b) Effect of bleached rhodopsin on signal amplification in rod visual receptors. Nature 345:537–539.

    Article  PubMed  CAS  Google Scholar 

  • Kahlert M, Hofmann KP (1991) Reaction rate and collisional efficiency of the rhodopsin-transducin system in intact retinal rods. Biophys J 59:375–386.

    Article  PubMed  CAS  Google Scholar 

  • Khorana HG (1992) Rhodopsin, photoreceptor of the rod cell. J Biol Chem 267:1–4.

    PubMed  CAS  Google Scholar 

  • Kelleher DJ, Johnson GL (1988) Transducin inhibition of light-dependent rhodopsin phosphorylation: evidence for βω subunit interaction with rhodopsin. Mol Pharm 34:452–460.

    CAS  Google Scholar 

  • Kibelbek J, Mitchell DC, Beach JM, Litman BJ (1991) Functional equivalence of metarhodopsin II and the Gt-activating form of photolyzed bovine rhodopsin. Biochemistry 30:6761–6768.

    Article  PubMed  CAS  Google Scholar 

  • König B (1989) Blitzlichtphotometrische Untersuchung der Interaktion des Photorezeptors Rhodopsin mit dem G-Protein Transducin: Identifizierung der relevanten Bereiche mit Hilfe monoklonaler Antikörper und synthetischer Peptide. Thesis, University of Freiburg.

    Google Scholar 

  • König B, Weite W, Hofmann KP (1989a) Photoactivation of rhodopsin and interaction with transducin in detergent micelles: effect of “doping” with steroid molecules. FEBS Lett 257:163–166.

    Article  PubMed  Google Scholar 

  • König B, Arendt A, McDowell JH, Kahlert M, Hargrave PA, Hofmann KP (1989b) Three cytoplasmic loops of rhodopsin interact with transducin. Proc Natl Acad Sci USA 86:6878–6882.

    Article  PubMed  Google Scholar 

  • Kohl B, Hofmann KP (1987) Temperature dependence of G-protein activation in photoreceptor membranes — transient extra metarhodopsin II on bovine disc membranes. Biophys J 52:271–277.

    Article  PubMed  CAS  Google Scholar 

  • Kreutz W, Siebert F, Hofmann KP (1984) Kinetic infrared spectorscopy and kinetic light-scattering — two new methods for studying fast trigger processes. In: Chapman D (ed) Biological membranes V. Academic, New York, pp 240–277.

    Google Scholar 

  • Kühn H (1980) Light-and GTP-regulated interaction of GTPase and other proteins with bovine photoreceptor membranes. Nature 283:587–589.

    Article  PubMed  Google Scholar 

  • Kühn H, Hargrave PA (1981) Light-induced binding of GTPase to bovine photoreceptor membranes: effects of limited proteolysis of the membranes. Biochemistry 20:2410–2417.

    Article  PubMed  Google Scholar 

  • Kühn H, Bennett N, Michel-Villaz M, Chabre M (1981) Interactions between photoexcited rhodopsin and GTP-binding protein: kinetic and stoichiometric analysis from light scattering changes. Proc Natl Acad Sci USA 78:6873–6877.

    Article  PubMed  Google Scholar 

  • Kühn H (1984) Interactions between photoexcited rhodopsin and light-activated enzymes in rods. In: Osborne N, Chader J (eds) Progress in retinal research. Pergamon, New York, pp 123–153.

    Google Scholar 

  • Lamb TD, Pugh EN Jr (1992) A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. J Physiol 449:719–758.

    PubMed  CAS  Google Scholar 

  • Liebman PA, Parker KR, Dratz EA (1987) The molecular mechanism of visual excitation and its relation to the structure and composition of the rod outer segment. Ann Rev Physiol 49:765–791.

    Article  CAS  Google Scholar 

  • Longstaff C, Calhoon RD, Rando RR (1986) Deprotonation of the Schiff base of rhodopsin is obligate in the activation of the G protein. Proc Natl Acad Sci USA 83:4209–4213.

    Article  PubMed  CAS  Google Scholar 

  • Matesic D, Liebman PA (1992) Spontaneous G-protein nucleotide exchange rate: implications for rod dark noise. Invest Ophthalm Vis Sci: ARVO abstract 2049 Morrison DF, O’Brien PJ, Pepperberg DR (1991) Depalmitylation with hydroxylamine alters the functional properties of rhodopsin. J Biol Chem 266:20118–20123.

    Google Scholar 

  • O’Dowd DF, Hnatovich, Regan JW, Leader WM, Caron MG, Lefkowitz RJ (1988) Site-directed mutagenesis of cytoplasmic domains of the human β-adrenergic receptor. Localization of regions involved in G protein-receptor coupling. J Biol Chem 262:15985–15992.

    Google Scholar 

  • Okamoto, T, Murayama, Y, Hayashi, Y, Inagaki M, Ogata E, Nishimoto I (1991) Identification of a Gs activator region of the β2-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation. Cell 67:723–730.

    Article  PubMed  CAS  Google Scholar 

  • Ovchinnikov YA (1982) Rhodopsin and bacteriorhodopsin: structure-function relationships. FEBS Lett 148:179–191.

    Article  PubMed  CAS  Google Scholar 

  • Palczewski K, Rispoli G, Detwiler PB (1992) The influence of arrestin (48K protein) and rhodopsin kinase on visual transduction. Neuron 8:117–126.

    Article  PubMed  CAS  Google Scholar 

  • Pepperberg DR, Kahlert M, Krause A, Hofmann KP (1988) Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors. Proc Natl Acad Sci USA 85:5531–5535.

    Article  PubMed  CAS  Google Scholar 

  • Panico J, Parkes JH, Liebman PA (1990) The effect of GDP on rod outer segment G-protein interactions. J Biol Chem 265:18922–18927.

    PubMed  CAS  Google Scholar 

  • Pepperberg DR, Cornwall MC, Kahlert M, Hofmann KP, Jin J, Jones GJ, Ripps H (1991) Light-dependent delay in the falling phase of the retinal rod photoresponse. Vis Neuroscience 8:9–18.

    Article  Google Scholar 

  • Pfister C, Kühn H, Chabre M (1983) Interaction between photoexcited rhodopsin and peripheral enzymes in frog retinal rods. Influence on the postmetarhodopsin II decay and phosphorylation rate of rhodopsin. Eur J Biochem 136:489–499.

    Article  PubMed  CAS  Google Scholar 

  • Robinson PR, Cohen GB, Zhukovsky EA, Oprian D (1992) Constitutive activation of rhodopsin by mutation of Lys296. FASEB J 6: A46.

    Google Scholar 

  • Sakmar TP, Franke RR, Khorana HG (1989) Glutamic acid-113 serves as the retinylidene Schiff base counterion in bovine rhodopsin. Proc Natl Acad Sci USA 86:8309–8313.

    Article  PubMed  CAS  Google Scholar 

  • Schleicher A, Hofmann KP (1987) Kinetic study on the equilibrium between membrane-bound and free photoreceptor G-protein. J Membr Biol 95:269–279.

    Google Scholar 

  • Schleicher A, Franke R, Hofmann KP, Finkelmann H, Weite W (1987) Deoxylysolecithin and a new biphenyl detergent as solutilizing agents for bovine rhodopsin — functional test by formation of metarhodopsin II and binding of G-protein. Biochemistry 26:5908–5916.

    Article  PubMed  CAS  Google Scholar 

  • Schleicher A, Kühn H, Hofmann KP (1989) Kinetics, binding constant, and activation energy of the 48-KDa protein-rhodopsin complex by extrametarhodopsin II. Biochemistry 28:1770–1775.

    Article  PubMed  CAS  Google Scholar 

  • Siebert F (1992) Infrared spectroscopic investigation of retinal proteins. In: Clark RJH, Hester RE (eds) Biomolecular spectroscopy. Advances in spectroscopy. Wiley, Chichester.

    Google Scholar 

  • Smith HG, Stubbs GW, Litman BJ (1975) The isolation and purification of osmotically intact discs from retinal rod outer segments. Exp Eye Res 20:211–217.

    Article  PubMed  Google Scholar 

  • Uhl R, Desel H, Ryba N, Wagner R (1987) J Biochem Biophys Meth 14:127–138.

    Article  PubMed  CAS  Google Scholar 

  • Vuong TM, Chabre M, Stryer L (1984) Millisecond activation of transducin in the cyclic nucleotide cascade of vision. Nature 311:659–661.

    Article  PubMed  CAS  Google Scholar 

  • Vuong TM, Chabre M (1991) Deactivation kinetics of the transduction cascade of vision. Proc Natl Acad Sci USA 88:9813–9817.

    Article  PubMed  CAS  Google Scholar 

  • Wagner R, Ryba NJP, Uhl R (1987) Rapid transducin deactivation in intact stacks of bovine rod outer segment disks as studied by light scattering techniques—arrestin requires additional soluble proteins for rapid quenching of rhodopsin catalytic activity. FEBS Lett 235:103–108.

    Article  Google Scholar 

  • Weitz CJ, Nathans J (1992) Histidine residues regulate the transition of photoexcited rhodopsin to its active conformation, metarhodopsin II. Neuron 8:465–472.

    Article  PubMed  CAS  Google Scholar 

  • Wilden U, Hall SW, Kühn H (1986) Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments. Proc Natl Acad Sci USA 83:1174–1178.

    Article  PubMed  CAS  Google Scholar 

  • Zhukovsky EA, Robinson PR, Oprian DD (1991) Transducin activation by rhodopsin without a covalent bond to the 11-cis-retinal chromophore. Science 251:558–560.

    Article  PubMed  CAS  Google Scholar 

  • Zundel G (to be published) Proton polarizability and proton transfer processes in hydrogen bonds and cation polarizabilities of other cation bonds — their importance to understand molecular processes in electrochemistry and biology. Trends Phys Chem.

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hofmann, K.P. (1993). Rhodopsin/G-Protein Interaction. In: Dickey, B.F., Birnbaumer, L. (eds) GTPases in Biology II. Handbook of Experimental Pharmacology, vol 108 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78345-6_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-78345-6_17

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78347-0

  • Online ISBN: 978-3-642-78345-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics