Protein-Cofaktor-Interactions in the Signaling State of Rhodopsin (SFB 498)


Vertebrate rhodopsin is a biological single photon detector and an archetype of a G-protein coupled receptor. A necessary condition for its function is the tight interaction in the ground state with the chromophore 11-cis-retinal. The ground state receptor is activated by light-induced cis/trans isomerization of the bound retinal. During the activation process, retinal plays a dual role, namely as a chromophore in the very fast initial photochemistry and, after relaxation of the photoexcited state, as an activating ligand. We distinguish three phases of the activation process: i) light induced cis/trans isomerization of the retinal, ii) thermal relaxation of the retinal-protein complex, and iii) the late equilibria which are affected by the interactions with the G-protein. In the active meta II state that results from these conversions, new interactions of the retinal with the protein are established. The goal is to understand this new interactions in the signaling state. In the last three years we developed new tools for this investigation, namely 1) formation of Meta II in the normal photolytic pathway but starting from artifical rhodopsins and ring-constrained retinal analogs, and 2) photolysis of the active state by blue light absorption. In both cases, our results have led to the working hypothesis of as yet unidentified pathways, which provide insight which of the possible interactions between the chromophore and the protein lead to receptor activation.
Head of Project:

PD Dr.rer.nat. Franz Bartl
Univ. Prof. Dr. Klaus-Peter Hofmann
Charité - Universitätsmedizin Berlin
Institute of Medical Physics and Biophysics CCM
Tel. 450-524170/524206
Fax 450-524952
franz.bartl@charite.de
Additional Head of Project:

Prof. Dr. K. P. Hofmann
Additional Member of Project:

Prof. H.W. Choe, Dr. rer. nat. E. Ritter
Begin/End of Project:

01/2000 - 12/2010
Funded by:

Deutsche Forschungsgemeinschaft e.V.
Publications:

Kuksa, F. Bartl, T. Maeda, G. Jang, E. Ritter,. M. Heck, J. P. van Hooser, Y. Liang, S. Filipek, M. Gelb, K.P. Hofmann, and K. Palczewski: Biochemical and physiological propertiesof rhodopsin regenerated with 11-cis-6-ring and 7-ring retinals. J. Biol. Chem. 276, 26148 26153, (2002). O.P. Ernst, F.J. Bartl: Active state of rhodopsin. ChemBiochem 3: 968-974, (2002). Ritter E., Zimmermann K., Heck M., Hofmann K.P. & Bartl F.J.:Transition of Rhodopsin into the Active Metarhodopsin II State Opens a New Light-induced Pathway Linked to Schiff Base Isomerization. J Biol Chem: 279(46) 48102-48111, (2004). Zimmermann K., Ritter E., Bartl F.J., Hofmann K.P. & Heck M.: Interaction with Transducin Depletes Metarhodopsin III: A regulated retinal storage in visual signal transduction? J Biol Chem: 279(46) 48112-48119, (2004). Bartl F.J., Fritze O., Ritter E., Herrmann R., Kuksa V., Palczewski K., Hofmann K.P. & Ernst O.P.: Partial agonism in a G Protein-coupled receptor: role of the retinal ring structure in rhodopsin activation. J Biol Chem: 280, 34259-34267, (2005).