Modulation of GDP release from transducin by the conserved Glu(134)-Arg(135) sequence in rhodopsin

A superfamily of seven-transmembrane helix receptors catalyzes GDP release from heterotrimeric guanine nucleotide-binding proteins (G proteins) to initiate the intracellular signaling cascade, The photoreceptor rhodopsin is a prototypical member of the superfamily that activates the retinal G protein transducin (G(t)), The cytoplasmic domain of rhodopsin binds and activates G(t), but residues that stimulate GDP release from G(t) have not been identified until now, We show here that the abnormal signal transduction phenotypes of several different mutations affecting the highly conserved Glu(134)-Arg(135) charge pair result from alteration of the GDP release step in the G(t) activation cascade, We propose that Glu(134) and Arg(135) constitute the site that directly provides the signal from rhodopsin to activate GDP release from G(t), Because the Glu/Asp-Arg sequence occurs at a topologically identical location in most of the seven-transmembrane helix receptors, we propose that these residues constitute a switch for signal transfer.