Crystal structure at 2.4 angstrom resolution of the complex of transducin beta gamma and its regulator, phosducin

The crystal structure of transducin's py subunits complexed with phosducin, which regulates G(t) beta gamma activity, has been solved to 2.4 Angstrom resolution. Phosducin has two domains that wrap around G(t) beta gamma to form an extensive interface. The N-terminal domain binds loops on the ''top'' G(t) beta surface, overlapping the G(t) alpha binding surface, explaining how phosducin blocks G(t) beta gamma's interaction with G(t) alpha. The C-terminal domain shows structural homology to thioredoxin and binds the outer strands of G(t) beta's seventh and first blades in a manner likely to disrupt G(t) beta gamma's normal orientation relative to the membrane and receptor. Phosducin's Ser-73, which when phosphorylated inhibits phosducin's function, points away from G(t) beta gamma, toward a large flexible loop. Thus phosphorylation is not likely to affect the interface directly, but rather indirectly through an induced conformational change.