Mastoparan, a 14-residue peptide, stimulates GDP/GTP exchange on G proteins in a manner strikingly analogous to that of agonist-bound receptors.


Mastoparan (MP), a cationic, amphiphilic tetradecapeptide isolated from wasp venom, is capable of directly stimulating the guanine nucleotide exchange reaction of the ?-subunit of animal heterotrimeric G proteins via a mechanism analogous to that of G protein coupled receptors. MP has been widely used to implicate G protein regulated processes in both plants and animals 1, 2, 3.

Structural Characteristics

Crystal structure of mastoparan from Polistes jadwagae (MP-PJ) at 1.2 Å resolution was solved in 2007. The crystals belong to the space group P2 (1) with eight molecules in an asymmetric unit. The crystals exist in the membrane-bound state of MP, all of the MP-PJ molecules are in possession of the alpha-helical conformation even in the absence of trifluorethanol or detergents in the crystallization system. The high-resolution structure enables the comparison of the conformation differences of MP-PJ with NMR results of other MP’s. Together with biochemical results, the crystal data suggested that the interactions between MP molecules play an important role in forming the alpha-helical conformation, which is highly related to their biological activities 4.

Mode of Action

MP treatment reported for plants include increases in cellular calcium ions, induction of an oxidative burst, stimulation of 1,4,5-inositol triphosphate turnover, and activation of phospholipase C, phospholipase D2, and myelin basic protein (MBP) kinases 5,6,7. MP induction of plant MAPK (Mitogen Activated Protein Kinase) signaling does not require the participation of either the Ga- or Gß-subunits of the plant heterotrimeric G proteins, but is reliant on reactive oxygen species (ROS), a cognate MAPKK (Mitogen Activated Protein Kinase Kinase), and influx of extracellular calcium ions. MP has a mode of action independent of a heterotrimeric G protein complex, regardless of the Ga-subunit composition 8.


MP and its active analogs have been extensively employed in studies of both plant and animal signaling networks. In plants, MP has the ability to activate a central signal pathway without requiring the involvement of a canonical heterotrimeric G protein.

MP induced activation of MAPKS (Mitogen Activated Protein Kinase Substrate) in Arabidopsis heterotrimeric Ga- or Gß loss-of-function genotypes but the Ga-subunit is the classical target of MP in animal cells 8.

It has been shown that MP is able to induce a rapid intracellular increase in calcium ion levels in both plants and animals. Calcium ions are also important in protein kinase signaling. MP induced activation of MAPK activity in tobacco is calcium-dependent 8.

MP stimulated human myocardial phosholipase C (PLC) approximately two fold with a half-maximal effect at approximately 2 µM and a maximal effect at 10 µM. The peptide did not alter the dependence of PLC on free calcium ions. In order to exclude non-specific effects of MP due to its amphiphilic properties, different MP derivatives were used as positive and negative controls. Mas17, an inactive MP analogue with physical properties very similar to MP, did not induce substantial PLC stimulation in human myocardial membranes. In contrast, Mas7, the most active MPderivative known, caused a more pronounced PLC activation compared with the mother compound indicating that the effect was sequence-specific. Human myocardial PLC stimulation was pertussis toxin-insensitive and could not be abolished by addition of excess a-subunits from purified retinal transducin or by excess GDP or GDPßS. To investigate whether MP stimulated PLC via pertussis toxin-insensitive aq, a deletion mutant of PLCß2 deficient of the site of interaction with aq-subunits was expressed in COS-1 cells. Both wild-type and mutant PLCß2 were found similarly sensitive to stimulation by MP 9.


1.     Higashijima T, Uzu S, Nakajima T, Ross EM (1988). Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins). J Biol Chem., 263:6491–6494.

2.     Ho¨ ller C, FreissmuthM, Nanoff C (1999). G proteins as drug targets. Cell Mol Life Sci., 55:257–270.

3.     Legendre L, Yueh YG, Crain R, Haddock N, Heinstein PF, Low PS (1993). Phospholipase C activation during elicitation of the oxidative burst in cultured plant cells. J Biol Chem., 268:24559–24563.

4.     Liu S, Wang F, Tang L, Gui W, Cao P, Liu X, Poon AW, Shaw PC, Jiang T (2007). Crystal structure of mastoparan from Polistes jadwagae at 1.2 A resolution. J Struct Biol., 160(1): 28-34.

5.     Chahdi A, Choi WS, Kim YM, Beaven M (2003). Mastoparan selectively activates phospholpase D2 in cell membranes. J Biol Chem., 278:12039-12045.

6.     Chahdi A, Daeffler L, Gies JP, Landry Y (1998). Drugs interacting with G protein a subunits: selectivity and perspectives. Fundam Clin Pharmacol., 12:12-132.

7.     Takahashi K, Isobe M, Muto S (1998). Mastoparan induces an increase in cytosolic calcium ion concentration and subsequent activation of protein kinases in tobacco suspension culture cells. Biochim Biophys Acta., 1401: 339–346.

8.     Miles GP, Samuel MA, Jones AM, Brian E. Ellis BE (2004). Mastoparan Rapidly Activates Plant MAP Kinase Signaling Independent of Heterotrimeric G Proteins. Plant Physiology.,134:1332-1336.

9.     Schnabel P, Gäs H, Nohr T,  Böhm M (1997 ). G protein-independent stimulation of human myocardial phospholipase C by mastoparan. Br J Pharmacol., 122(1):31-36.

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