Alamethicin-like behaviour of new 18-residue peptaibols, trichorzins PA. Role of the C-terminal amino-alcohol in the ion channel forming activity.
The influences of peptide length, absence of a Glx (Gln/Glu) residue and the C-terminal amino alcohol on liposome permeabilization and ion-channel characteristics in planar lipid bilayers were examined with two 18-residue peptaibols, PA V and PA IX. As compared to the 20-residue alamethicin, both peptides belonging to the newly isolated trichorzin family, lack a proline in the N-terminal part and one of the two Gln/Glu residues in the C-terminal part of the sequence. The two analogues studied here differ among themselves in their C-terminal amino alcohol (tryptophanol for PA V and phenylalaninol for PA IX). These alpha-helical peptaibols modify to a similar extent the permeability of liposomes, as measured by leakage of a previously entrapped fluorescent probe. Monitoring tryptophanol fluorescence, a greater embedment of the peptide PA V is observed in cholesterol-free bilayers. Macroscopic conductance studies for PA V and PA IX display alamethicin-like current-voltage curves, with a similar voltage dependence, but a smaller mean number of monomers per conducting aggregate is estimated for the tryptophanol analogue, PA V. Single-channel recordings indicate faster current fluctuations for PA IX, while amplitude histograms show lower conductance levels for PA V. Apart from underlining the role of the mismatch between helix length and bilayer hydrophobic thickness, these results stress that the C-terminal tryptophanol favours a stabilization of the conducting aggregates.
Duval
D
D
Laboratoire de Chimie des Substances Naturelles, URA 401 CNRS, GDR 1153 CNRS, IFR 63 CNRS-INSERM, Muséum National d'Histoire Naturelle, 63 rue Buffon, 75231 Paris Cedex 05, France.
Cosette
P
P
Rebuffat
S
S
Duclohier
H
H
Bodo
B
B
Molle
G
G
D000408:Alamethicin / Q000737:chemistry / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002942:Circular Dichroism; D005456:Fluorescent Dyes; D007473:Ion Channels / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers; D008081:Liposomes; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D000900:Anti-Bacterial Agents; D005456:Fluorescent Dyes; D007473:Ion Channels; D008051:Lipid Bilayers; D008081:Liposomes; D000408:Alamethicin