Membrane pores induced by magainin.
Magainin, found in the skin of Xenopus laevis, belongs to a broad class of antimicrobial peptides which kill bacteria by permeabilizing the cytoplasmic membrane but do not lyse eukaryotic cells. The 23-residue peptide has been shown to form an amphiphilic helix when associated with membranes. However, its molecular mechanism of action has been controversial. Oriented circular dichroism has detected helical magainin oriented perpendicular to the plane of the membrane at high peptide concentrations, but Raman, fluorescence, differential scanning calorimetry, and NMR all indicate that the peptide is associated with the head groups of the lipid bilayer. Here we show that neutron in-plane scattering detects pores formed by magainin 2 in membranes only when a substantial fraction of the peptide is oriented perpendicular to the membrane. The pores are almost twice as large as the alamethicin pores. On the basis of the in-plane scattering data, we propose a toroidal (or wormhole) model, which differs from the barrel-stave model of alamethicin in that the lipid bends back on itself like the inside of a torus. The bending requires a lateral expansion in the head group region of the bilayer. Magainin monomers play the role of fillers in the expansion region thereby stabilizing the pore. This molecular configuration is consistent with all published magainin data.
Ludtke
S J
SJ
Physics Department, Rice University, Houston, Texas 77005-1892, USA.
He
K
K
Heller
W T
WT
Harroun
T A
TA
Yang
L
L
Huang
H W
HW
D000408:Alamethicin / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D017666:Deuterium Oxide; D008051:Lipid Bilayers / Q000378:metabolism; D054806:Magainins; D008563:Membrane Lipids / Q000378:metabolism; D008954:Models, Biological; D008968:Molecular Conformation; D009502:Neutrons; D010455:Peptides / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D012542:Scattering, Radiation; D012867:Skin / Q000737:chemistry; D029867:Xenopus Proteins; D014982:Xenopus laevis
D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D054806:Magainins; D008563:Membrane Lipids; D010455:Peptides; D010743:Phospholipids; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D000408:Alamethicin; D017666:Deuterium Oxide