Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Logo for

Science 288 (5474): 2209-2212

Copyright © 2000 by the American Association for the Advancement of Science

Movement of Retinal Along the Visual Transduction Path

Babak Borhan, 1 Maria L. Souto, 1 Hiroo Imai, 2 Yoshinori Shichida, 2 Koji Nakanishi 1*

Movement of the ligand/receptor complex in rhodopsin (Rh) has been traced. Bleaching of diazoketo rhodopsin (DK-Rh) containing 11-cis-3-diazo-4-oxo-retinal yields batho-, lumi-, meta-I-, and meta-II-Rh intermediates corresponding to those of native Rh but at lower temperatures. Photoaffinity labeling of DK-Rh and these bleaching intermediates shows that the ionone ring cross-links to tryptophan-265 on helix F in DK-Rh and batho-Rh, and to alanine-169 on helix D in lumi-, meta-I-, and meta-II-Rh intermediates. It is likely that these movements involving a flip-over of the chromophoric ring trigger changes in cytoplasmic membrane loops resulting in heterotrimeric guanine nucleotide-binding protein (G protein) activation.

1 Department of Chemistry, Columbia University, New York, NY 10027, USA.
2 Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
*   To whom correspondence should be addressed. E-mail: kn5{at}columbia.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mechanism of Signal Propagation upon Retinal Isomerization: Insights from Molecular Dynamics Simulations of Rhodopsin Restrained by Normal Modes.
B. Isin, K. Schulten, E. Tajkhorshid, and I. Bahar (2008)
Biophys. J. 95, 789-803
   Abstract »    Full Text »    PDF »
Curvature and Hydrophobic Forces Drive Oligomerization and Modulate Activity of Rhodopsin in Membranes.
A. V. Botelho, T. Huber, T. P. Sakmar, and M. F. Brown (2006)
Biophys. J. 91, 4464-4477
   Abstract »    Full Text »    PDF »
Insights into the Cholecystokinin 2 Receptor Binding Site and Processes of Activation.
M. R. Paillasse, C. Deraeve, P. de Medina, L. Mhamdi, G. Favre, M. Poirot, and S. Silvente-Poirot (2006)
Mol. Pharmacol. 70, 1935-1945
   Abstract »    Full Text »    PDF »
Local peptide movement in the photoreaction intermediate of rhodopsin.
H. Nakamichi and T. Okada (2006)
PNAS 103, 12729-12734
   Abstract »    Full Text »    PDF »
From The Cover: Crosstalk in G protein-coupled receptors: Changes at the transmembrane homodimer interface determine activation.
W. Guo, L. Shi, M. Filizola, H. Weinstein, and J. A. Javitch (2005)
PNAS 102, 17495-17500
   Abstract »    Full Text »    PDF »
Partial Agonism in a G Protein-coupled Receptor: ROLE OF THE RETINAL RING STRUCTURE IN RHODOPSIN ACTIVATION.
F. J. Bartl, O. Fritze, E. Ritter, R. Herrmann, V. Kuksa, K. Palczewski, K. P. Hofmann, and O. P. Ernst (2005)
J. Biol. Chem. 280, 34259-34267
   Abstract »    Full Text »    PDF »
Does the Chromophore's Ring Move after Photoexcitation of Rhodopsin?.
T. G. Ebrey and M. Kumauchi (2005)
Biophys. J. 88, L41-L42
   Abstract »    Full Text »    PDF »
Structural Mimicry in Class A G Protein-coupled Receptor Rotamer Toggle Switches: THE IMPORTANCE OF THE F3.36(201)/W6.48(357) INTERACTION IN CANNABINOID CB1 RECEPTOR ACTIVATION.
S. D. McAllister, D. P. Hurst, J. Barnett-Norris, D. Lynch, P. H. Reggio, and M. E. Abood (2004)
J. Biol. Chem. 279, 48024-48037
   Abstract »    Full Text »    PDF »
A Model of Inverse Agonist Action at Thyrotropin-Releasing Hormone Receptor Type 1: Role of a Conserved Tryptophan in Helix 6.
X. Lu, W. Huang, S. Worthington, P. Drabik, R. Osman, and M. C. Gershengorn (2004)
Mol. Pharmacol. 66, 1192-1200
   Abstract »    Full Text »    PDF »
Critical Role of Transmembrane Segment Zinc Binding in the Structure and Function of Rhodopsin.
A. Stojanovic, J. Stitham, and J. Hwa (2004)
J. Biol. Chem. 279, 35932-35941
   Abstract »    Full Text »    PDF »
Coupling of retinal isomerization to the activation of rhodopsin.
A. B. Patel, E. Crocker, M. Eilers, A. Hirshfeld, M. Sheves, and S. O. Smith (2004)
PNAS 101, 10048-10053
   Abstract »    Full Text »    PDF »
Identification of CRALBP Ligand Interactions by Photoaffinity Labeling, Hydrogen/Deuterium Exchange, and Structural Modeling.
Z. Wu, A. Hasan, T. Liu, D. C. Teller, and J. W. Crabb (2004)
J. Biol. Chem. 279, 27357-27364
   Abstract »    Full Text »    PDF »
Gonadotropin-Releasing Hormone Receptors.
R. P. Millar, Z.-L. Lu, A. J. Pawson, C. A. Flanagan, K. Morgan, and S. R. Maudsley (2004)
Endocr. Rev. 25, 235-275
   Abstract »    Full Text »    PDF »
First Principles Predictions of the Structure and Function of G-Protein-Coupled Receptors: Validation for Bovine Rhodopsin.
R. J. Trabanino, S. E. Hall, N. Vaidehi, W. B. Floriano, V. W. T. Kam, and W. A. Goddard 3rd (2004)
Biophys. J. 86, 1904-1921
   Abstract »    Full Text »    PDF »
Differential dynamics in the G protein-coupled receptor rhodopsin revealed by solution NMR.
J. Klein-Seetharaman, N. V. K. Yanamala, F. Javeed, P. J. Reeves, E. V. Getmanova, M. C. Loewen, H. Schwalbe, and H. G. Khorana (2004)
PNAS 101, 3409-3413
   Abstract »    Full Text »    PDF »
Vertebrate ultraviolet visual pigments: Protonation of the retinylidene Schiff base and a counterion switch during photoactivation.
A. K. Kusnetzow, A. Dukkipati, K. R. Babu, L. Ramos, B. E. Knox, and R. R. Birge (2004)
PNAS 101, 941-946
   Abstract »    Full Text »    PDF »
Mutational Analysis and Molecular Modeling of the Binding Pocket of the Metabotropic Glutamate 5 Receptor Negative Modulator 2-Methyl-6-(phenylethynyl)-pyridine.
P. Malherbe, N. Kratochwil, M.-T. Zenner, J. Piussi, C. Diener, C. Kratzeisen, C. Fischer, and R. H. P. Porter (2003)
Mol. Pharmacol. 64, 823-832
   Abstract »    Full Text »    PDF »
Mutational Analysis and Molecular Modeling of the Allosteric Binding Site of a Novel, Selective, Noncompetitive Antagonist of the Metabotropic Glutamate 1 Receptor.
P. Malherbe, N. Kratochwil, F. Knoflach, M.-T. Zenner, J. N. C. Kew, C. Kratzeisen, H. P. Maerki, G. Adam, and V. Mutel (2003)
J. Biol. Chem. 278, 8340-8347
   Abstract »    Full Text »    PDF »
Molecular Dynamics Investigation of Primary Photoinduced Events in the Activation of Rhodopsin.
J. Saam, E. Tajkhorshid, S. Hayashi, and K. Schulten (2002)
Biophys. J. 83, 3097-3112
   Abstract »    Full Text »    PDF »
Biochemical and Physiological Properties of Rhodopsin Regenerated with 11-cis-6-Ring- and 7-Ring-retinals.
V. Kuksa, F. Bartl, T. Maeda, G.-F. Jang, E. Ritter, M. Heck, J. P. Van Hooser, Y. Liang, S&l.;a. Filipek, M. H. Gelb, et al. (2002)
J. Biol. Chem. 277, 42315-42324
   Abstract »    Full Text »    PDF »
Rhodopsin with 11-cis-Locked Chromophore Is Capable of Forming an Active State Photoproduct.
G. Fan, F. Siebert, M. Sheves, and R. Vogel (2002)
J. Biol. Chem. 277, 40229-40234
   Abstract »    Full Text »    PDF »
beta 2 Adrenergic Receptor Activation. MODULATION OF THE PROLINE KINK IN TRANSMEMBRANE 6 BY A ROTAMER TOGGLE SWITCH.
L. Shi, G. Liapakis, R. Xu, F. Guarnieri, J. A. Ballesteros, and J. A. Javitch (2002)
J. Biol. Chem. 277, 40989-40996
   Abstract »    Full Text »    PDF »
Conformation of Ligands Bound to the Muscarinic Acetylcholine Receptor.
H. Furukawa, T. Hamada, M. K. Hayashi, T. Haga, Y. Muto, H. Hirota, S. Yokoyama, K. Nagasawa, and M. Ishiguro (2002)
Mol. Pharmacol. 62, 778-787
   Abstract »    Full Text »    PDF »
A 5-HT4 Receptor Transmembrane Network Implicated in the Activity of Inverse Agonists but Not Agonists.
L. Joubert, S. Claeysen, M. Sebben, A.-S. Bessis, R. D. Clark, R. S. Martin, J. Bockaert, and A. Dumuis (2002)
J. Biol. Chem. 277, 25502-25511
   Abstract »    Full Text »    PDF »
Lipid-facing correlated mutations and dimerization in G-protein coupled receptors.
P. R. Gouldson, M. K. Dean, C. R. Snell, R. P. Bywater, G. Gkoutos, and C. A. Reynolds (2001)
Protein Eng. Des. Sel. 14, 759-767
   Abstract »    Full Text »    PDF »
Rhodopsin: Structural Basis of Molecular Physiology.
S. T. Menon, M. Han, and T. P. Sakmar (2001)
Physiol Rev 81, 1659-1688
   Abstract »    Full Text »    PDF »
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor.
K. Palczewski, T. Kumasaka, T. Hori, C. A. Behnke, H. Motoshima, B. A. Fox, I. L. Trong, D. C. Teller, T. Okada, R. E. Stenkamp, et al. (2000)
Science 289, 739-745
   Abstract »    Full Text »
Signaling States of Rhodopsin. ABSORPTION OF LIGHT IN ACTIVE METARHODOPSIN II GENERATES AN ALL-TRANS-RETINAL BOUND INACTIVE STATE.
F. J. Bartl, E. Ritter, and K. P. Hofmann (2001)
J. Biol. Chem. 276, 30161-30166
   Abstract »    Full Text »    PDF »
Mechanism of Rhodopsin Activation as Examined with Ring-constrained Retinal Analogs and the Crystal Structure of the Ground State Protein.
G.-F. Jang, V. Kuksa, S. Filipek, F. Bartl, E. Ritter, M. H. Gelb, K. P. Hofmann, and K. Palczewski (2001)
J. Biol. Chem. 276, 26148-26153
   Abstract »    Full Text »    PDF »
Transmembrane Domains 4 and 7 of the M1 Muscarinic Acetylcholine Receptor Are Critical for Ligand Binding and the Receptor Activation Switch.
Z.-L. Lu, J. W. Saldanha, and E. C. Hulme (2001)
J. Biol. Chem. 276, 34098-34104
   Abstract »    Full Text »    PDF »
Control of Conformational Equilibria in the Human B2 Bradykinin Receptor. MODELING OF NONPEPTIDIC LIGAND ACTION AND COMPARISON TO THE RHODOPSIN STRUCTURE.
J. Marie, E. Richard, D. Pruneau, J.-L. Paquet, C. Siatka, R. Larguier, C. Ponce, P. Vassault, T. Groblewski, B. Maigret, et al. (2001)
J. Biol. Chem. 276, 41100-41111
   Abstract »    Full Text »    PDF »

ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)