The mammalian G proteins transduce information from extracellular signals, including neurotransmitters, hormones and sensory stimuli, into regulation of effector enzymes or ion channels within cells. Triggered by appropriate extracellular signals, receptor proteins specifically activate members of the G protein family by catalysing replacement of GDP by GTP at the guanine nucleotide binding site. Like the receptor proteins1, the heterotrimeric G proteins exhibit impressive structural similarities2,3, suggesting that all receptor-G protein interactions use homologous structural elements and a single molecular mechanism. Topologically equivalent portions of each G protein may therefore interact with the appropriate receptor. We recently predicted the secondary structure of a composite G protein α-chain and proposed that a predicted amphipathic α-helix at the extreme carboxy-terminus of the polypeptide directly contacts receptors4. This proposal has now been confirmed by sequencing complementary DNAs of the gene that encodes the α-chain (αs) of the stimulatory regulator (Gs) of adenylyl cyclase in wild-type cells and in a mutant mouse S49 lymphoma cell line, unc, in which Gs cannot be activated by hormone receptors5. The sequences reveal a point mutation in the unc gene that substitutes a proline residue for an arginine near the carboxy-terminus of the αs-polypeptide. Expression of recombinant αs-unc in genetically αs-deficient S49 cells reproduces the unc phenotype.
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