Source: 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 Molecular basis for interactions of G protein betagamma subunits with effectors. Science. 1998 May 22;280(5367):1271-4.
Abstract
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.
PMID: 9596582 | EndNote Citation
- Effector Interactions with the b-Subunit of Heterotrimeric G Protein
- Mutations that inhibit stimulation of adenylyl cyclase 2
- Mutations that either enhance (dark color) or inhibit (light color) stimulation of beta-adrenergic receptor kinase
- Mutations that either increase (dark color) or decrease (light color) inhibition of calcium channels
- Mutations that inhibit stimulation of potassium channels
- Mutations that either increase (dark color) or decrease (light color) stimulation of phospholipase C-beta 2
- Residues important for Ga binding
- Residues important for interactions with rhodopsin
- Sidechains of Gb residues implicated in effector binding