title: Signalling states of photoactivated rhodopsin.
abstract: In microseconds after photoexcitation, rhodopsin forms the Meta I intermediate from lumirhodopsin. In this conversion, contacts between retinal and the apoprotein are formed, which result in a defined arrangement of donor and acceptor groups for proton translocations. A system of protonation-dependent coupled equilibria is now adopted, comprising Meta intermediates I, II and III, and their isospectral subforms. Some Meta states were identified as signalling states, in which the receptor interacts with transducin (Gt), rhodopsin kinase (RK) and arrestin. The binding of Gt or arrestin shifts the equilibrium to Meta II, while RK does not, indicating exposure of the RK binding site(s) before Meta II is formed. On contact with the activated receptor, each signalling protein responds with a conformational change, which transforms it into a functionally active state. The bell-shaped pH/rate profiles which are seen for the activation of both the G protein and the receptor kinase, indicate the necessary protonation and deprotonation of groups with different pKa. The right wing of the profile reflects the formation of the protonated subconformation (termed MIIb) of Meta II. For the interaction with Gt, recent work suggests a 'sequential fit' mechanism, involving the recognition of the C-terminal peptide of the Gt alpha subunit and of the farnesylated C-terminus of the gamma subunit. Isolated peptides derived from these portions of the G protein mimic the left wing of the pH/rate profile. We discuss the sequential fit as a time-ordered sequence of microscopic recognition and conformational interlocking in the interaction with the G protein.
authors.affiliation: Institut für Medizinische Physik und Biophysik, Medizinische Fakultät Charité, Humboldt-Universität zu Berlin, Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D012243:Rhodopsin / Q000737:chemistry / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D012243:Rhodopsin