A molecular mechanism for the phosphorylation-dependent regulation of heterotrimeric G proteins by phosducin

Visual signal transduction is a nearly noise-free process that is exquisite ly well regulated over a wide dynamic range of light intensity. A key compo nent in dark/light adaptation is phosducin, a phosphorylatable protein that modulates the amount of transducin heterotrimer (G(t)alpha beta gamma) ava ilable through sequestration of the py subunits (G(t)beta gamma). The struc ture of the phosphophosducin/G(t)beta gamma complex combined with mutationa l and biophysical analysis provides a stereochemical mechanism for the regu lation of the phosducin-G(t)beta gamma interaction. Phosphorylation of seri ne 73 causes an order-to-disorder transition of a 20-residue stretch, inclu ding the phosphorylation site, by disrupting a helix-capping motif. This tr ansition disrupts phosducin's interface with G(t)beta gamma, leading to the release of unencumbered G(t)beta gamma, which reassociates with the membra ne and G(t)beta gamma to form a signaling-competent G(t)alpha beta gamma he terotrimer.