Antimicrobial peptides (AMPs) are an important component of innate immunity and have generated considerable interest as a potential new class of antibiotic. The biological activity of AMPs is strongly influenced by peptide-membrane interactions; however, for many of these peptides the molecular details of how they disrupt and/or translocate across target membranes are not known. CM15 is a linear, synthetic hybrid AMP composed of the first seven residues of the cecropin A and residues 2–9 of the bee venom peptide mellitin. Previous studies have shown that upon membrane binding CM15 folds into an a-helix with its helical axis aligned parallel to the bilayer surface and have implicated the formation of 2.2–3.8 nm pores in its bactericidal activity. Here we report site-directed spin labeling electron paramagnetic resonance studies examining the behavior of CM15 analogs labeled with a methanethiosulfonate spin label (MTSL) and a brominated MTSL as a function of increasing peptide concentration and utilize phospholipid-analog spin labels to assess the effects of CM15 binding and accumulation on the physical properties of membrane lipids. We find that as the concentration of membrane-bound CM15 is increased the N-terminal domain of the peptide becomes more deeply immersed in the lipid bilayer. Only minimal changes are observed in the rotational dynamics of membrane lipids, and changes in lipid dynamics are confined primarily to near the membrane surface. However, the accumulation of membrane-bound CM15 dramatically increases accessibility of lipid-analog spin labels to the polar relaxation agent, nickel (II) ethylenediaminediacetate, suggesting an increased permeability of the membrane to polar solutes. These results are discussed in relation to the molecular mechanism of membrane disruption by CM15.
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|Titolo:||Membrane Insertion and Bilayer Perturbation by Antimicrobial Peptide CM15|
|Citazione:||Pistolesi, S., Pogni, R., & Feix, J.B. (2007). Membrane Insertion and Bilayer Perturbation by Antimicrobial Peptide CM15. BIOPHYSICAL JOURNAL, 93, 1651-1660.|
|Appare nelle tipologie:||1.1 Articolo in rivista|