A surface on the G protein beta-subunit involved in interactions with adenylyl cyclases.
Receptor activation of heterotrimeric G proteins dissociates G alpha from the G betagamma complex, allowing both to regulate effectors. Little is known about the effector-interaction regions of G betagamma. We had used molecular modeling to dock a peptide encoding the region of residues 956-982 of adenylyl cyclase (AC) 2 onto Gbeta to identify residues on Gbeta that may interact with effectors. Based on predictions from the model, we synthesized peptides encoding sequences of residues 86-105 (Gbeta 86-105) and 115-135 (Gbeta 115-135) from Gbeta. The Gbeta 86-105 peptide inhibited G betagamma stimulation of AC2 and blocked G betagamma inhibition of AC1 and by itself inhibited calmodulin-stimulated AC1, thus displaying partial agonist activity. Substitution of Met-101 with Asn in this peptide resulted in the loss of both the inhibitory and partial agonist activities. Most activities of the Gbeta 115-135 peptide were similar to those of Gbeta 86-105 but Gbeta 115-135 was less efficacious in blocking G betagamma inhibition of AC1. Substitution of Tyr-124 with Val in the Gbeta 115-135 peptide diminished all of its activities. These results identify the region encoded by amino acids 84-143 of Gbeta as a surface that is involved in transmitting signals to effectors.
Chen
Y
Y
Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Weng
G
G
Li
J
J
Harry
A
A
Pieroni
J
J
Dingus
J
J
Hildebrandt
J D
JD
Guarnieri
F
F
Weinstein
H
H
Iyengar
R
R
D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002417:Cattle; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D046911:Macromolecular Substances; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism
D046911:Macromolecular Substances; D010446:Peptide Fragments; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases