Barrel-stave model or toroidal model? A case study on melittin pores

Transmembrane pores induced by amphiphilic peptides, including melittin, ar e often modeled with the barrel-stave model after the alamethicin pore. We examine this assumption on melittin by using two methods, oriented circular dichroism (OCD) for detecting the orientation of melittin helix and neutro n scattering for detecting transmembrane pores. OCD spectra of melittin wer e systematically measured. Melittin can orient either perpendicularly or pa rallel to a lipid bilayer, depending on the physical condition and the comp osition of the bilayer. Transmembrane pores were detected when the helices oriented perpendicularly to the plane of the bilayers, not when the helices oriented parallel to the bilayers. The evidence that led to the barrel-sta ve model for alamethicin and that to the toroidal model for magainin were r eviewed. The properties of melittin pores are closely similar to that of ma gainin but unlike that of alamethicin. We conclude that, among naturally pr oduced peptides that we have investigated, only alamethicin conforms to the barrel-stave model. Other peptides, including magainins, melittin and prot egrins, all appear to induce transmembrane pores that conform to the toroid al model in which the lipid monolayer bends continuously through the pore s o that the water core is lined by both the peptides and the lipid headgroup s.