FAMILY OF G-PROTEIN ALPHA-CHAINS - AMPHIPATHIC ANALYSIS AND PREDICTED STRUCTURE OF FUNCTIONAL DOMAINS

The G proteins transduce hormonal and other signals into regulation of enzymes such as adenylyl cyclase and retinal cGMP phosphodiesterase. Each G protein contains an .alpha. subuit that binds and hydrolyzes guanine nucleotides and interacts with .beta..gamma. subunits and specific receptor and effector proteins. Amphipatic and secondary structure analysis of the primary sequences of five different .alpha. chains (bovine .alpha.s, .alpha.t1, and .alpha.t2, mouse .alpha.i, and rat .alpha.0) predicted the secondary structure of a composite .alpha. chain (.alpha.avg). The .alpha. chains contain four short regions of sequence homologous to regions in the GDP binding domain of bacterial elongation factor Tu (EF-Tu). Similarities between the predicted secondary structures of these regions in .alpha.avg and the known secondary structure of EF-Tu allowed us to construct a three-dimensional model of the GDP binding domain of .alpha.avg. Identification of the GDP binding domain of .alpha.avg defined three additional domains in the composite polypeptide. The first includes the amino terminal 41 residues of .alpha.avg, with a predicted amphipathic .alpha. helical structure; this domain may control binding of the .alpha. chains to the .beta..gamma. complex. The second domain, containing predicted .beta. strands and .alpha. helices, several of which are strongly amphipathic, probably contains of sequences responsible for interaction of .alpha. chains with effector enzymes. The predicted structure of the third domain, containing the carboxy terminal 100 amino acids, is predominantly .beta. sheet with an amphipathic .alpha. helix at the carboxy terminus. We propose that this domain is responsible for receptor binding. Our model should help direct further experiments into the structure and function of the G protein .alpha. chain.