The specificity of the stress-produced
antimicrobial peptide cateslytin to
fungi membranes has been investigated using complex membrane models made of
zwitterionic and negatively charged
lipids,
cholesterol, or
ergosterol. Noninvasive solid-state
NMR of
deuterated neutral and negatively charged
lipids, together with
IR spectroscopy, afforded following both changes in
membrane fluidity and in
peptide secondary structure. Cateslytin, by adopting an aggregated antiparallel beta-sheeted structure at membrane interfaces, induces a fluid/rigid membrane separation on ergosterol-containing models only. This effect is accounted for by a 2-fold electronic interaction: attractive dipole-dipole between basic
arginine residues and negatively charged
lipid head groups, and attractive cation-pi between
arginine and the conjugated pi
electrons of the
ergosterol fused-ring system. This complex leads to fluid/
thinner membranes that
laterally separate out from rigid/thicker membranes that are not bound by cateslytin. The boundary defects occurring between domains span several angstroms, as probed by
NMR of perdeuterated
lipids, and are proposed to trigger
peptide permeation through membranes. The intrinsic greater
membrane fluidity of
ergosterol/acidic
lipid components in
fungi is shown to be one of the key factors for specific cateslytin biological action.
