Family of G protein α chains: amphipathic analysis and predicted structure of functional domains

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Abstract
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 α subunit that binds and hydrolyzes guanine nucleotides and interacts with βγ subunits and specific receptor and effector proteins. Amphipathic and secondary structure analysis of the primary sequences of five different α chains (bovine αs, αt1 and αt2, mouse αi, and rat αo) predicted the secondary structure of a composite α chain (αavg). The α 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 αavg and the known secondary structure of EF-Tu allowed us to construct a three-dimensional model of the GDP binding domain of αavg. Identification of the GDP binding domain of αavg defined three additional domains in the composite polypeptide. The first includes the amino terminal 41 residues of αavg, with a predicted am phipathic α helical structure; this domain may control binding of the α chains to the βγ complex. The second domain, containing predicted β strands and α helices, several of which are strongly amphipathic, probably contains sequences responsible for interaction of α chains with effector enzymes. The predicted structure of the third domain, containing the carhoxy terminal 100 amino acids, is predominantly β sheet with an amphipathic α helix at the carboxy terminus. We propose that this domain is reponsible for receptor binding. Our model should help direct further experiments into the structure and function of the G protein α chain.