title: Chromophore structural changes in rhodopsin from nanoseconds to microseconds following pigment photolysis.
abstract: Rhodopsin is a prototypical G protein-coupled receptor that is activated by photoisomerization of its 11-cis-retinal chromophore. Mutant forms of rhodopsin were prepared in which the carboxylic acid counterion was moved relative to the positively charged chromophore Schiff base. Nanosecond time-resolved laser photolysis measurements of wild-type recombinant rhodopsin and two mutant pigments then were used to determine reaction schemes and spectra of their early photolysis intermediates. These results, together with linear dichroism data, yielded detailed structural information concerning chromophore movements during the first microsecond after photolysis. These chromophore structural changes provide a basis for understanding the relative movement of rhodopsin's transmembrane helices 3 and 6 required for activation of rhodopsin. Thus, early structural changes following isomerization of retinal are linked to the activation of this G protein-coupled receptor. Such rapid structural changes lie at the heart of the pharmacologically important signal transduction mechanisms in a large variety of receptors, which use extrinsic activators, but are impossible to study in receptors using diffusible agonist ligands.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jäger
authors.forename: J W
authors.initials: JW
authors.lastname: Lewis
authors.forename: T A
authors.initials: TA
authors.lastname: Zvyaga
authors.forename: I
authors.initials: I
authors.lastname: Szundi
authors.forename: T P
authors.initials: TP
authors.lastname: Sakmar
authors.forename: D S
authors.initials: DS
authors.lastname: Kliger
mesh_terms: D000818:Animals; D002417:Cattle; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D010782:Photolysis; D012243:Rhodopsin / Q000737:chemistry* / Q000235:genetics; D013997:Time Factors
chemical_list: D012243:Rhodopsin