Molecular basis for interactions of G protein betagamma subunits with effectors.
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.
Ford
C E
CE
Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA.
Skiba
N P
NP
Bae
H
H
Daaka
Y
Y
Reuveny
E
E
Shekter
L R
LR
Rosal
R
R
Weng
G
G
Yang
C S
CS
Iyengar
R
R
Miller
R J
RJ
Jan
L Y
LY
Lefkowitz
R J
RJ
Hamm
H E
HE
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D001665:Binding Sites; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D054799:Phospholipase C beta; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011487:Protein Conformation; D012243:Rhodopsin / Q000494:pharmacology; D015398:Signal Transduction; D015293:Transducin / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D051552:beta-Adrenergic Receptor Kinases
D015220:Calcium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C034809:GNAT1 protein, human; D007527:Isoenzymes; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D006153:Guanosine Diphosphate; D000246:Adenosine Diphosphate Ribose; D012243:Rhodopsin; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D010738:Type C Phospholipases; C518036:PLCB2 protein, human; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin; D000262:Adenylyl Cyclases; C100622:adenylyl cyclase 2