This chapter discusses regulation of G-protein activation by mastoparans and other cationic properties. Mastoparan, Ile-Asn-Leu-Lys-Ala-Leu-Ala-Ala-Leu-Ala-Lys-Lys-Ile- Leu-amide (MP), activates G proteins by catalyzing Guanosine-5'-triphosphate (GTP)/Leu-amide (MP), by catalyzing GTP/GDP exchange, the mechanism of action of G-protein-coupled receptors. Like receptors, MP accelerates guanine nucleotide exchange at micromolar Mg2+, it does not alter hydrolysis of bound GTP, its action is markedly potentiated by G-protein fly subunits, and it is blocked by pertussis toxin-catalyzed ADP-ribosylation of the target α subunit. The MPs are prototypical of a wide variety of amphiphilic, cationic peptides that activates G proteins. MP is a natural component of wasp venom, and at least seven MP analogs are produced by different species. Regulatory activity requires that a G-protein-stimulating peptide be both amphiphilic and cationic. Helix-breaking residues or charged residues on what should be the hydrophobic face of the helix both diminish activity dramatically. Mas17, with a lysyl residue on the hydrophobic side of the helix, is a commercially available negative control for experiments where MP is used to alter G-protein activation.
ASJC Scopus subject areas
- Molecular Biology