Magainin 2, a natural antibiotic from frog skin, forms ion channels in lipid bilayer membranes.
We have examined the ion channel forming properties of magainin 2 by incorporating the peptide into artificial lipid bilayers held under voltage clamp. Magainin 2 increased lipid bilayer conductance in a concentration dependent manner with a Hill coefficient of 1.7. The magainin 2 conductance was selective for monovalent cations over anions with a ratio of 5:1 and had both voltage-sensitive and -insensitive components. Two structurally related but antibiotically less potent analogues, magainin 1 and Z-12, also increased lipid bilayer conductance with a similar ion selectivity but these peptides were less potent than magainin 2. We propose that the weak cation selectivity of the magainin channels can be accounted for by the inclusion of negatively charged lipids in the channel complex and suggest two possible structures for such a channel. The ionophoric properties of these peptides are likely to be proximal to their antibiotic activities.
Cruciani
R A
RA
Laboratory of Neurophysiology, NINDS, NIH, Bethesda, MD.
Barker
J L
JL
Durell
S R
SR
Raghunathan
G
G
Guy
H R
HR
Zasloff
M
M
Stanley
E F
EF
D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008051:Lipid Bilayers / Q000378:metabolism*; D054806:Magainins; D008954:Models, Biological; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D029867:Xenopus Proteins
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D007473:Ion Channels; D008051:Lipid Bilayers; D054806:Magainins; D010455:Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; C053300:magainin 1 peptide, Xenopus