Coupling of Protonation Switches During Rhodopsin Activation†

Two protonation switches control rhodopsin activation in membranes.

Activation of the G protein-coupled receptor (GPCR) rhodopsin is initiated by light-induced isomerization of the retinal ligand, which triggers 2 protonation switches in the conformational transition to the active receptor state Meta II. The first switch involves disruption of an interhelical salt bridge by internal proton transfer from the retinal protonated Schiff base (PSB) to its counterion...

Protonation of the Retinal Chromophore in Rhodopsin

Coupling of retinal isomerization to the activation of rhodopsin.

Activation of the visual pigment rhodopsin is caused by 11-cis to -trans isomerization of its retinal chromophore. High-resolution solid-state NMR measurements on both rhodopsin and the metarhodopsin II intermediate show how retinal isomerization disrupts helix interactions that lock the receptor off in the dark. We made 2D dipolar-assisted rotational resonance NMR measurements between (13)C-la...

Activation of rhodopsin kinase.

The present study confirms our original assertion that peptides corresponding to the C-terminal sequence of rhodopsin are phosphorylated by rhodopsin kinase (RK), but only in the presence of photo-activated rhodopsin [Rho*, which is functionally equivalent to metarhodopsin II (Meta II)]. Under optimized conditions, the extent of peptide phosphorylation reached up to 60% that of Rho*. Rho* phosp...

Mechanism of rhodopsin kinase activation.

The role of the cytoplasmic loops and C-terminal region of bovine rhodopsin (Rho) in binding and activating rhodopsin kinase was investigated. The ability of various enzymatically truncated forms of photolyzed rhodopsin (Rho*) to stimulate rhodopsin kinase activity was quantified. Following endopeptidase Asp-N cleavage of all phosphorylation sites on the C-terminal, the resulting truncated Rho*...