Action of antimicrobial peptides: two-state model.
The argument and experimental evidence are presented for a two-state model that explains the action of both helical and beta-sheet antimicrobial peptides after they bind to the plasma membranes of cells. Each peptide has two distinct physical states of binding to lipid bilayers. At low peptide-to-lipid ratios (P/L), the peptide tends to adsorb in the lipid headgroup region in a functionally inactive state. At a P/L above a threshold value P/L, the peptide forms a multiple-pore state that is lethal to a cell. The susceptibility of a cell to an antimicrobial peptide depends on the value of P/L that is determined by the lipid composition of the cell membrane. This model provides plausible explanations for the experimental findings that the susceptibility of different bacteria to a peptide is not directly correlated to its binding affinity, different peptides preferentially kill different pathogens, and peptides exhibit varying levels of lytic activity against different eukaryotic cells.
Department of Physics, Rice University, Houston, Texas 77251, USA. hwhuang@rice.edu
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D000327:Adsorption; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004563:Electrochemistry; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides; D017433:Protein Structure, Secondary
D000900:Anti-Bacterial Agents; D010455:Peptides