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J. Biol. Chem., Vol. 283, Issue 49, 33854-33857, December 5, 2008

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On the Mechanism of Pore Formation by Melittin^*

From the Department of Biochemistry, the Groningen Biomolecular Sciences and Biotechnology Institute and the Zernike Institute for Advanced Materials, University of Groningen, 9747AG The Netherlands

The mechanism of pore formation of lytic peptides, such as melittin from bee venom, is thought to involve binding to the membrane surface, followed by insertion at threshold levels of bound peptide. We show that in membranes composed of zwitterionic lipids, i.e. phosphatidylcholine, melittin not only forms pores but also inhibits pore formation. We propose that these two modes of action are the result of two competing reactions: direct insertion into the membrane and binding parallel to the membrane surface. The direct insertion of melittin leads to pore formation, whereas the parallel conformation is inactive and prevents other melittin molecules from inserting, hence preventing pore formation.

Received for publication, July 8, 2008

^* This work was supported by the Dutch Science Foundation (NWO, Grant ALW-814.02.002) and the Zernike Institute for Advanced Materials. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Nijenborgh 4, 9747 AG, Groningen, The Netherlands. Tel.: 31-50-363-4190; Fax: 31-50-363-4165; E-mail: b.poolman{at}rug.nl.

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