Abstract
We investigate the mode of action of Cateslytin, an antimicrobial peptide, on zwitterionic biomembranes by performing numerical simulations and electrophysiological measurements on membrane vesicles. Using this natural beta-sheet antimicrobial peptide secreted during stress as a model we show that a single peptide is able to form a stable membrane pore of 1 nm diameter of 0.25 nS conductance found both from calculation and electrical measurements. The resulting structure does not resemble the barrel-stave or carpet models earlier predicted, but is very close to that found in the simulation of alpha-helical peptides. Based on the simulation of a mutated peptide and the effects of small external electric fields, we conclude that electrostatic forces play a crucial role in the process of pore formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antimicrobial Cationic Peptides / chemistry
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Antimicrobial Cationic Peptides / metabolism
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Antimicrobial Cationic Peptides / pharmacology*
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Cattle
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Cell Membrane / chemistry
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Chromogranin A / chemistry
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Chromogranin A / metabolism
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Chromogranin A / pharmacology*
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Dimyristoylphosphatidylcholine / metabolism
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Electroporation
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Hydrophobic and Hydrophilic Interactions
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Sequence Data
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Patch-Clamp Techniques
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology*
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Porosity / drug effects
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Protein Structure, Secondary
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Static Electricity*
Substances
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Antimicrobial Cationic Peptides
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Chromogranin A
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Peptide Fragments
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chromogranin A (344-358)
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Dimyristoylphosphatidylcholine