A Site on Rod G Protein α Subunit That Mediates Effector Activation

• Published in: Science (American Association for the Advancement of Science) 1992-05, Vol.256 (5059), p.1031-1033
• Main Authors: Rarick, Helen M., Artemyev, Nikolai O., Hamm, Heidi E.
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - metabolism; 3',5'-cyclic-nucleotide phosphodiesterase; activation; Amino Acid Sequence; Animals; Binding Sites; Biological and medical sciences; Cattle; Cell physiology; Chimeras; Chromatography, High Pressure Liquid; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; G proteins; Gels; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - physiology; guanine nucleotide-binding protein; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Guanosine Diphosphate - metabolism; Guanosine Triphosphate - metabolism; Inhibitory concentration 50; interaction; Macromolecular Substances; Molecular and cellular biology; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Photoreceptors; Protein Conformation; Protons; Receptors; rods; sites; transducin; Ungulates; Vision, photoreception
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1317058

The heterotrimeric guanine nucleotide binding proteins (G proteins) are activated by sensory or hormone receptors. In turn, the G proteins activate effector proteins such as adenylyl cyclase, cyclic guanosine 3′,5′-monophosphate phosphodiesterase (cGMP PDE), phospholipase C, and potassium and calcium ion channels by mechanisms that are poorly understood. A site on the α subunit of the G protein transducin ($\alpha_t$) has been identified that interacts with and activates cGMP phosphodiesterase, the effector enzyme in rod photoreceptors. A 22-amino acid peptide, corresponding to residues 293 to 314 from the COOH-terminal region of $\alpha_t$, fully mimicked $\alpha_t$ and potently activated PDE. This region is adjacent to the receptor activation domain; thus, the ά subunit of this G protein has a site for interaction with both its effector and receptor that maps near the COOH-terminus.