On the mechanism of pore formation by melittin.
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.
van den Bogaart
Geert
G
Department of Biochemistry, the Groningen Biomolecular Sciences and Biotechnology Institute and the Zernike Institute for Advanced Materials, University of Groningen, 9747AG The Netherlands.
Guzmán
Jeanette Velásquez
JV
Mika
Jacek T
JT
Poolman
Bert
B
D000818:Animals; D001514:Bee Venoms; D001516:Bees; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008555:Melitten / Q000737:chemistry* / Q000378:metabolism; D008968:Molecular Conformation; D010713:Phosphatidylcholines / Q000737:chemistry; D017434:Protein Structure, Tertiary; D013499:Surface Properties
D001514:Bee Venoms; D005452:Fluoresceins; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D008555:Melitten; C017251:1,2-oleoylphosphatidylcholine; C007740:fluorexon