title: Mutations probe structure and function of G-protein alpha chains.
abstract: The molecular genetic approach has just begun to provide hints of answers to some of the questions posed at the outset of this paper. We have some idea of which portions of the alpha chain of Gs interact with receptors and effectors, and we guess that the same is true of corresponding regions of other alpha chains. We have a tantalizing hint that points to a key region of alpha s that is necessary for the conformational change induced by binding GTP, and the vague outline of a hypothesis regarding the mechanism by which receptors release GDP from its binding site on the alpha chain. The alpha chain region (domain) that interacts with beta gamma remains unknown. The tenuous quality of all these hints and hypotheses is obvious, and at least in the short term, frustrating. Even the present level of our understanding, however, is impressive in comparison with what was known of G-protein function only 5 years ago. Now we can pose much more precise questions and hope that a combination of the molecular genetic approach with biophysical probes of structure will provide satisfying answers.
authors.affiliation: Department of Pharmacology, University of California, San Francisco 94143-0450.
authors.forename: H R
authors.initials: HR
authors.lastname: Bourne
authors.forename: S B
authors.initials: SB
authors.lastname: Masters
authors.forename: R T
authors.initials: RT
authors.lastname: Miller
authors.forename: K A
authors.initials: KA
authors.lastname: Sullivan
authors.forename: W
authors.initials: W
authors.lastname: Heideman
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D046911:Macromolecular Substances; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins