title: Functional differences in the beta gamma complexes of transducin and the inhibitory guanine nucleotide regulatory protein.
abstract: We have examined the mechanism of inhibition of adenylate cyclase using the purified alpha and beta gamma subunits of bovine brain inhibitory guanine nucleotide regulatory protein (Ni) (i.e., alpha i and beta gamma N) and bovine retinal transducin (alpha T and beta gamma T) in reconstituted phospholipid vesicle systems. The addition of beta gamma N or beta gamma T to lipid vesicles containing the pure stimulatory guanine nucleotide regulatory protein (Ns) from human erythrocytes as well as a resolved preparation of the catalytic moiety (C) of bovine caudate adenylate cyclase results in significant inhibition of guanine nucleotide stimulated cyclase activity (80-90%). The inhibition by these beta gamma subunit complexes appears to fully account for the inhibitory effects observed with holo-Ni or holotransducin. A variety of structure-function comparisons of the beta gamma N and beta gamma T complexes were performed in order to further probe the molecular mechanisms involved in the inhibitory pathway. Whereas the beta subunits of beta gamma N and beta gamma T appear to be very similar, if not identical, on the basis of comparisons of their gel electrophoretic mobility and immunological cross-reactivity, clear differences exist in the apparent structures of gamma N and gamma T. Interestingly, functional differences are observed in the effectiveness of these two beta gamma complexes to inhibit adenylate cyclase activity. Specifically, while both beta gamma N and beta gamma T are capable of effecting significant levels of inhibition of the guanine nucleotide stimulated activities, the beta gamma N complex is consistently more potent than beta gamma T in inhibiting these activities.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002417:Cattle; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012160:Retina / Q000502:physiology; D013329:Structure-Activity Relationship; D015293:Transducin
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011943:Receptors, Adrenergic, beta; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D015293:Transducin; D007545:Isoproterenol