Molecular basis for interactions of G protein betagamma subunits with effectors.

Ford CE, Skiba NP, Bae H, Daaka Y, Reuveny E, Shekter LR, Rosal R, Weng G, Yang CS, Iyengar R, Miller RJ, Jan LY, Lefkowitz RJ, Hamm HE
Science. 1998 280 (5367): 1271-4

PMID: 9596582 · DOI:10.1126/science.280.5367.1271

Both the alpha and betagamma subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins) communicate signals from receptors to effectors. Gbetagamma subunits can regulate a diverse array of effectors, including ion channels and enzymes. Galpha subunits bound to guanine diphosphate (Galpha-GDP) inhibit signal transduction through Gbetagamma subunits, suggesting a common interface on Gbetagamma subunits for Galpha binding and effector interaction. The molecular basis for interaction of Gbetagamma with effectors was characterized by mutational analysis of Gbeta residues that make contact with Galpha-GDP. Analysis of the ability of these mutants to regulate the activity of calcium and potassium channels, adenylyl cyclase 2, phospholipase C-beta2, and beta-adrenergic receptor kinase revealed the Gbeta residues required for activation of each effector and provides evidence for partially overlapping domains on Gbeta for regulation of these effectors. This organization of interaction regions on Gbeta for different effectors and Galpha explains why subunit dissociation is crucial for signal transmission through Gbetagamma subunits.

MeSH Terms (23)

Adenosine Diphosphate Ribose Adenylyl Cyclases beta-Adrenergic Receptor Kinases Binding Sites Calcium Channels Cell Line Cyclic AMP-Dependent Protein Kinases G Protein-Coupled Inwardly-Rectifying Potassium Channels GTP-Binding Proteins Guanosine Diphosphate Heterotrimeric GTP-Binding Proteins Humans Isoenzymes Models, Molecular Mutation Phospholipase C beta Potassium Channels Potassium Channels, Inwardly Rectifying Protein Conformation Rhodopsin Signal Transduction Transducin Type C Phospholipases

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