RECEPTOR AND BETA-GAMMA BINDING-SITES IN THE ALPHA-SUBUNIT OF THE RETINAL G-PROTEIN TRANSDUCIN

Transmembrane receptors for hormones, neurotransmitters, light, and od orants mediate their cellular effects by activating heterotrimeric gua nine nucleotide-binding proteins (G proteins), Crystal structures have revealed contact surfaces between G protein subunits, but not the sur faces or molecular mechanism through which G alpha beta gamma responds to activation by transmembrane receptors, Such a surface was identifi ed from the results of testing 100 mutant alpha subunits of the retina l G protein transducin for their ability to interact with rhodopsin, S ites at which alanine substitutions impaired this interaction mapped t o two distinct G alpha surfaces: a beta gamma-binding surface and a pu tative receptor-interacting surface. On the basis of these results a m echanism for receptor-catalyzed exchange of guanosine diphosphate for guanosine triphosphate is proposed.