Pertussis toxin-catalyzed ADP-ribosylation of adenylate cyclase. Effects of guanyl nucleotides and rhodopsin.
Hormonal inhibition of adenylate cyclase is mediated by inhibitory receptors and a guanyl nucleotide-binding coupling protein, termed Gi. Similarly, transducin (T), a guanyl nucleotide-binding protein, mediates activation of cGMP phosphodiesterase by the retinal photon receptor, rhodopsin. Gi and T are both heterotrimers consisting of alpha, beta, and gamma subunits; Gi alpha and G beta are similar to T alpha and T beta, respectively. T alpha hydrolyzes GTP in the presence of photolyzed, but not dark, rhodopsin and T beta gamma. Gi alpha and G beta gamma substituted for T alpha and T beta gamma to yield active hybrid complexes, T alpha G beta gamma and Gi alpha T beta gamma. In the absence of T components, rhodopsin-dependent GTPase activity of Gi alpha G beta gamma was observed. Pertussis toxin ADP-ribosylates both T alpha and Gi alpha; ADP-ribosylation of Gi alpha was negligible in the absence of G beta gamma. With G beta gamma, photolyzed, but not dark, rhodopsin unhibited ADP-ribosylation of Gi alpha. In the presence of G beta gamma and photolyzed rhodopsin, GDP and GDP beta S, but not Gpp(NH)p and GTP gamma S, increased the ADP-ribosylation of Gi alpha. The requirements for ADP-ribosylation of Gi alpha by pertussis toxin were similar to those for ADP-ribosylation of T alpha. Rhodopsin appears to interact with Gi in a manner similar to the inhibitory hormone receptors; photolyzed rhodopsin, the active species, corresponds to the agonist-occupied receptor, while dark rhodopsin, the inactive species, can be equated to the free receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006150:Guanine Nucleotides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D037342:Pertussis Toxin; D011487:Protein Conformation; D011817:Rabbits; D012168:Retinal Pigments / Q000494:pharmacology*; D012243:Rhodopsin / Q000494:pharmacology*; D015293:Transducin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D006150:Guanine Nucleotides; D008565:Membrane Proteins; D012168:Retinal Pigments; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D012243:Rhodopsin; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D015293:Transducin; D000262:Adenylyl Cyclases