A mutation that prevents GTP-dependent activation of the alpha chain of Gs.
Membrane-bound G proteins carry information from receptors on the outside of cells to effector proteins inside cells. The alpha subunits of these heterotrimeric proteins bind and hydrolyse GTP and control the specificity of interactions with receptor and effector elements. Signalling by G proteins involves a cycle in which the inactive alpha beta gamma-GDP complex dissociates to produce alpha*-GTP, which is capable of activating the effector enzyme or ion channel; the alpha*-GTP complex hydrolyses bound GTP and reassociates with beta gamma to form the inactive complex. We have characterized a mutation that interrupts this GTP-driven cycle in alpha s, the alpha-chain of Gs, the G protein that stimulates adenylyl cyclase. The mutation converts a glycine to an alanine residue in the presumed GDP-binding domain of alpha s. The location and biochemical consequences of this mutation suggest a common mechanism by which binding of GTP or ATP may induce changes in the conformation of a number of nucleoside triphosphate binding proteins.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008223:Lymphoma; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D011487:Protein Conformation / Q000187:drug effects; D014357:Trypsin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017607:Aluminum Compounds; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D004247:DNA; D000535:Aluminum; D014357:Trypsin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium; D005459:Fluorides; C032311:aluminum fluoride