Transducin-alpha C-terminal peptide binding site consists of C-D and E-F loops of rhodopsin

The binding of heterotrimeric GTP-binding proteins (G-proteins) to serpentine receptors involves dependent contacts. We have deduced the points of interaction between mutant bovine rhodopsins and alpha(t)-(340350), a peptide corresponding to the C terminus of the cu subunit (cu,) of bovine retinal G-protein, transducin , Direct binding of alpha(t)-(340350) to rhodopsin stabilizes the activated metarhodopsin II state (M II), consequently uncoupling the rhodopsin-transducin interaction, This peptide action requires two segments on the cytoplasmic domain of rhodopsin: the Tyr(136)-Val(137) Val(138)-Val(139) sequence on the C-D loop and the Glu(247) Lys(248)-Glu(249)-Val(250)-Thr(251) sequence on the E-F loop, We propose that a tertiary interaction of these two loop regions forms a pocket for binding the cu, C terminus of the transducin during light transduction in vivo. In most G-proteins, the C termini of alpha subunits are important for interaction with receptors, and, in several serpentine receptors, regions similar to those in rhodopsin are essential for G-protein activation, indicating that the interaction described here may be a generally applicable mode of G-protein binding in signal transduction.