Bilayer lipid composition modulates the activity of dermaseptins, polycationic antimicrobial peptides.
The primary targets of defense peptides are plasma membranes, and the induced irreversible depolarization is sufficient to exert antimicrobial activity although secondary modes of action might be at work. Channels or pores underlying membrane permeabilization are usually quite large with single-channel conductances two orders of magnitude higher than those exhibited by physiological channels involved, e.g., in excitability. Accordingly, the ion specificity and selectivity are quite low. Whereas, e.g., peptaibols favor cation transport, polycationic or basic peptides tend to form anion-specific pores. With dermaseptin B2, a 33 residue long and mostly alpha-helical peptide isolated from the skin of the South American frog Phyllomedusa bicolor, we found that the ion specificity of its pores induced in bilayers is modulated by phospholipid-charged headgroups. This suggests mixed lipid-peptide pore lining instead of the more classical barrel-stave model. Macroscopic conductance is nearly voltage independent, and concentration dependence suggests that the pores are mainly formed by dermaseptin tetramers. The two most probable single-channel events are well resolved at 200 and 500 pS (in 150 mM NaCl) with occasional other equally spaced higher or lower levels. In contrast to previous molecular dynamics previsions, this study demonstrates that dermaseptins are able to form pores, although a related analog (B6) failed to induce any significant conductance. Finally, the model of the pore we present accounts for phospholipid headgroups intercalated between peptide helices lining the pore and for one of the most probable single-channel conductance.
Institut de Physiologie et de Biologie Cellulaires (Pôle Biologie Santé), UMR 6187 CNRS-Université de Poitiers, 40 Avenue du Recteur Pineau, 86022, Poitiers, France. herve.duclohier@univ-poitiers.fr
Hervé
H
Duclohier
D029845:Amphibian Proteins / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D003198:Computer Simulation; D004553:Electric Conductivity; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry*; D016062:Porosity
D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010743:Phospholipids; C485283:dermaseptin B2, Phyllomedusa bicolor