Barrel-Stave Model or Toroidal Model? A Case Study on Melittin Pores

Abstract

Transmembrane pores induced by amphiphilic peptides, including melittin, are 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 neutron scattering for detecting transmembrane pores. OCD spectra of melittin were systematically measured. Melittin can orient either perpendicularly or parallel to a lipid bilayer, depending on the physical condition and the composition 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-stave model for alamethicin and that to the toroidal model for magainin were reviewed. The properties of melittin pores are closely similar to that of magainin but unlike that of alamethicin. We conclude that, among naturally produced peptides that we have investigated, only alamethicin conforms to the barrel-stave model. Other peptides, including magainins, melittin and protegrins, all appear to induce transmembrane pores that conform to the toroidal model in which the lipid monolayer bends continuously through the pore so that the water core is lined by both the peptides and the lipid headgroups.

Energetics of Pore Formation Induced by Membrane Active Peptides

“…Both gave the same results in this study. Yang et al (35) also found no difference between Sigma melittin and pure synthetic melittin in this type of study as long as there was no added Ca 2+ in the sample. Poly(ethylene glycol) (PEG20000) was purchased from Merk Co. (Hohenfrunn, Germany).…”

“…Melittin, magainin, protegrin, and perhaps most cationic antimicrobial peptides form toroidal pores (35). In this paper, alamethicin and melittin are used to study these two types of pores.…”

Intracellular trafficking of nonviral vectors

“…Melittin forms an amphipathic a-helix in aqueous solution and interacts with lipid membranes through a positively charged cluster (KRKR). The mechanism by which melittin inserts into the membrane and disrupts it has been vigorously studied, and evidence supports a model in which it forms toroidal pores 129,130 (Figure 3a). In this model, the peptides induce perturbations in the membrane and bend it so that the top and bottom layers of the bilayer join contiguously at the pore wall.…”

Interaction and Lipid-Induced Conformation of Two Cecropin−Melittin Hybrid Peptides Depend on Peptide and Membrane Composition

“…The antimicrobial peptides studied are known to adopt an R-helical structure in the presence of membranes. 15,21,23,25,60 The importance of this structure for antimicrobial activity has been a subject of debate, whereas the influence of membrane charge on peptide-membrane interaction is relevant for the development of selective antibiotics. 5,20,30,49,61 From the present work, we can conclude that DSC provided a detailed insight intosand differentiation betweensthe interactions of two cecropin A-melittin hybrid peptides with three lipid model systems.…”

“…16 Other investigations on microorganisms confirmed that, generally, antimicrobial peptides exert their activity by permeabilizing the plasma membrane. 3,11,17,18 Alternative mechanisms of action have been proposed for some antimicrobial peptides, 4,[19][20][21][22][23][24][25][26][27][28] and the requirements for peptide antimicrobial activity have also been extensively discussed. 3,[29][30][31][32][33] Differential scanning calorimetry (DSC) has emerged as a most valuable tool to study peptide-membrane interactions.…”