Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs to a family of homologous coupling proteins that also includes G, and G1, the regulatory proteins of adenylate cyclase. Here we report the cDNA sequence and deduced amino acid sequence of transducin's a subunit (Ta). The cDNA was isolated, by screening with an antibody probe, from a bovine retinal cDNA library in the expression vector Xgtll. The 2.2-kilobase cDNA insert hybridized to a single 2.6-kilobase poly(A)+ RNA species present in extracts of bovine retina but not of bovine heart, liver, or brain. The nucleotide sequence of the cDNA revealed an open reading frame long enough to encode the entire 39-kDa T. polypeptide. The polypeptide sequence deduced from the cDNA would be composed of 350 amino acids and have a molecular weight of 39,971. Portions of the sequence matched reported amino acid sequences of Ta tryptic fragments, including sites specificlly ADP-ribosylated by cholera and pertussis toxins. The predicted sequence also includes four segments, ranging from 11 to 19 residues in length, that exhibit significant homology to sequences of GTP-binding proteins, including the ras proteins of man and yeast and the elongation factors of ribosomal protein synthesis in bacteria, EF-G and EF-Tu. In combination with previous functional studies of tryptic fragments of Ta, the deduced amino acid sequence makes it possible to predict which portions of the polypeptide interact with other molecules involved in retinal phototransduction.Transducin, a guanine nucleotide binding protein of retinal rod cells, mediates the activation of a cyclic GMP phosphodiesterase (PDEase) in response to photoexcitation of rhodopsin (1). Each photolyzed rhodopsin (R*) molecule activates hundreds of transducin molecules by catalyzing the exchange of GTP for GDP at transducin's guanine nucleotide binding site. The activated transducin-GTP complex in turn stimulates the hydrolysis of many cGMP molecules by PDEase. Hydrolysis of bound GTP returns transducin to its inactive state.Transducin contains three subunits, a, ,B, and y, whose sizes are 39, 35, and =8 kDa, respectively. Transducin exhibits striking structural and functional homologies to the stimulatory (Gs) and inhibitory (Gi) coupling proteins of hormone-sensitive adenylate cyclase. Each protein is a heterotrimer in which the respective subunits exhibit similar amino acid compositions and proteolytic peptide maps (2). In each case, the protein's interaction with an excited signal detector (rhodopsin or hormone receptor) triggers dissociation of the /3y complex from the a subunit, which then alters activity of the effector molecule (PDEase or adenylate cyclase) (1, 3).After hydrolysis of GTP bound to the a subunit, the P-y
