DIRECT ACTIVATION OF GTP-BINDING PROTEINS BY VENOM PEPTIDES THAT CONTAIN CATIONIC CLUSTERS WITHIN THEIR ALPHA-HELICAL STRUCTURES

Direct interactions of venom peptides that contained a cysteine-stabilized α-helical motif within their internal molecules with αβγ-trimeric GTP-binding proteins (G proteins) were studied in reconstituted phospholipid vesicles. Mast cell-degranulating (MCD) peptide stimulated the steady-state rate of GTP hydrolysis catalyzed by the reconstituted G proteins. Synthetic D-MCD peptide, the optical isomer of MCD peptide, was also effective in the activation of G proteins as L-MCD peptide. The stimulations by L- and D-peptides were both abolished in G proteins that had been ADP-ribosylated by pertussis toxin. Charybdotoxin also stimulated, though slightly, the GTPase activity of G proteins. Such a stimulation was, however, not observed upon the incubation of G proteins with other venom peptides such as apamin, sarafotoxin and endothelin. Thus, in comparison of the amino acid sequences of their venom peptides, the extent of the activation of G proteins appeared to be correlated with the number of basic amino acid residues around the α-helix. These results suggest that cationic clusters at one side of the α-helical surface are more important in the direct activation of G proteins than a specific, α-helical structure. © 1991.