| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 26, 19713-19718, June 30, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the The G-protein-coupled receptor rhodopsin is
activated by photoconversion of its covalently bound ligand
11-cis-retinal to the agonist
all-trans-retinal. After light-induced isomerization and
early photointermediates, the receptor reaches a
G-protein-dependent equilibrium between active and inactive
conformations distinguished by the protonation of key opsin residues.
In this report, we study the role of the 9-methyl group of retinal, one
of the crucial steric determinants of light activation. We find that
when this group is removed, the protonation equilibrium is strongly
shifted to the inactive conformation. The residually formed active
species is very similar to the active form of normal rhodopsin,
metarhodopsin II. It has a deprotonated Schiff base, binds to the
retinal G-protein transducin, and is favored at acidic pH. Our data
show that the normal proton transfer reactions are inhibited in
9-demethyl rhodopsin but are still mandatory for receptor activation.
We propose that retinal and its 9-methyl group act as a scaffold for
opsin to adjust key proton donor and acceptor side chains for the
proton transfer reactions that stabilize the active conformation. The mechanism may also be applicable to related receptors and may thus
explain the partial agonism of certain ligands.
Signaling States of Rhodopsin
RETINAL PROVIDES A SCAFFOLD FOR ACTIVATING PROTON TRANSFER
SWITCHES*
,,
, and
Institut für Medizinische Physik und
Biophysik, Humboldt Universität zu Berlin,
Universtitätsklinikum Charité, Schumannstrasse 20-21,
10098 Berlin and the § Max-Planck-Institut für
Strahlenchemie, Stiftstrasse 34-36, 45470 Mülheim an der Ruhr,
Germany
*
This work was supported by Grants Sfb 449 (to O. P. E. and K. P. H.) and Sfb 498 (to K. P. H.)
from the Deutsche Forschungsgemeinschaft.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed. Tel.:
49-30-2802-6141; Fax: 49-30-2802-6377; E-mail: kph@charite.de or
oliver.ernst{at}charite.de.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Berthold, S. P. Tsunoda, O. P. Ernst, W. Mages, D. Gradmann, and P. Hegemann Channelrhodopsin-1 Initiates Phototaxis and Photophobic Responses in Chlamydomonas by Immediate Light-Induced Depolarization PLANT CELL, June 1, 2008; 20(6): 1665 - 1677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Knierim, K. P. Hofmann, W. Gartner, W. L. Hubbell, and O. P. Ernst Rhodopsin and 9-Demethyl-retinal Analog: EFFECT OF A PARTIAL AGONIST ON DISPLACEMENT OF TRANSMEMBRANE HELIX 6 IN CLASS A G PROTEIN-COUPLED RECEPTORS J. Biol. Chem., February 22, 2008; 283(8): 4967 - 4974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. P. Ernst, P. A. S. Murcia, P. Daldrop, S. P. Tsunoda, S. Kateriya, and P. Hegemann Photoactivation of Channelrhodopsin J. Biol. Chem., January 18, 2008; 283(3): 1637 - 1643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Knierim, K. P. Hofmann, O. P. Ernst, and W. L. Hubbell Sequence of late molecular events in the activation of rhodopsin PNAS, December 18, 2007; 104(51): 20290 - 20295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. P. Ernst, V. Gramse, M. Kolbe, K. P. Hofmann, and M. Heck Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit PNAS, June 26, 2007; 104(26): 10859 - 10864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ritter, M. Elgeti, K. P. Hofmann, and F. J. Bartl Deactivation and Proton Transfer in Light-induced Metarhodopsin II/Metarhodopsin III Conversion: A TIME-RESOLVED FOURIER TRANSFORM INFRARED SPECTROSCOPIC STUDY J. Biol. Chem., April 6, 2007; 282(14): 10720 - 10730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Ridge and K. Palczewski Visual Rhodopsin Sees the Light: Structure and Mechanism of G Protein Signaling J. Biol. Chem., March 30, 2007; 282(13): 9297 - 9301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Estevez, P. Ala-Laurila, R. K. Crouch, and M. C. Cornwall Turning Cones Off: the Role of the 9-Methyl Group of Retinal in Red Cones J. Gen. Physiol., December 1, 2006; 128(6): 671 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Bartl, O. Fritze, E. Ritter, R. Herrmann, V. Kuksa, K. Palczewski, K. P. Hofmann, and O. P. Ernst Partial Agonism in a G Protein-coupled Receptor: ROLE OF THE RETINAL RING STRUCTURE IN RHODOPSIN ACTIVATION J. Biol. Chem., October 7, 2005; 280(40): 34259 - 34267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Y. Chae, J.-H. Kim, W.-J. Park, Y.-G. Kim, H.-Y. Yun, N. S. Kwon, M.-J. Im, and K. J. Baek Distinct pH Modulation for Dual Function of G{alpha}h (Transglutaminase II) J. Biochem., March 1, 2005; 137(3): 407 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Janz and D. L. Farrens Role of the Retinal Hydrogen Bond Network in Rhodopsin Schiff Base Stability and Hydrolysis J. Biol. Chem., December 31, 2004; 279(53): 55886 - 55894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ritter, K. Zimmermann, M. Heck, K. P. Hofmann, and F. J. Bartl Transition of Rhodopsin into the Active Metarhodopsin II State Opens a New Light-induced Pathway Linked to Schiff Base Isomerization J. Biol. Chem., November 12, 2004; 279(46): 48102 - 48111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Patel, E. Crocker, M. Eilers, A. Hirshfeld, M. Sheves, and S. O. Smith Coupling of retinal isomerization to the activation of rhodopsin PNAS, July 6, 2004; 101(27): 10048 - 10053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Fritze, S. Filipek, V. Kuksa, K. Palczewski, K. P. Hofmann, and O. P. Ernst Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation PNAS, March 4, 2003; 100(5): 2290 - 2295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Heck, S. A. Schadel, D. Maretzki, F. J. Bartl, E. Ritter, K. Palczewski, and K. P. Hofmann Signaling States of Rhodopsin. FORMATION OF THE STORAGE FORM, METARHODOPSIN III, FROM ACTIVE METARHODOPSIN II J. Biol. Chem., January 24, 2003; 278(5): 3162 - 3169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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. Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor Science, August 4, 2000; 289(5480): 739 - 745. [Abstract] [Full Text]
|
|
|
|
|
|
F. J. Bartl, E. Ritter, and K. P. Hofmann Signaling States of Rhodopsin. ABSORPTION OF LIGHT IN ACTIVE METARHODOPSIN II GENERATES AN ALL-TRANS-RETINAL BOUND INACTIVE STATE J. Biol. Chem., August 3, 2001; 276(32): 30161 - 30166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-F. Jang, V. Kuksa, S. Filipek, F. Bartl, E. Ritter, M. H. Gelb, K. P. Hofmann, and K. Palczewski Mechanism of Rhodopsin Activation as Examined with Ring-constrained Retinal Analogs and the Crystal Structure of the Ground State Protein J. Biol. Chem., July 6, 2001; 276(28): 26148 - 26153. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
