The cyclic antimicrobial peptide RTD-1 induces stabilized lipid-peptide domains more efficiently than its open-chain analogue.
The effects of a mammalian cyclic antimicrobial peptide, rhesus theta defensin 1 (RTD-1) and its open chain analogue (oRTD-1), on the phase behaviour and structure of model membrane systems (dipalmitoyl phosphatidylcholine, DPPC and dipalmitoyl phosphatidylglycerol, DPPG) were studied. The increased selectivity of RTD-1 for anionic DPPG over zwitterionic DPPC was shown by differential scanning calorimetry. RTD-1, at a molar peptide-lipid ratio of 1:100, induced considerable changes in the phase behaviour of DPPG, but not of DPPC. The main transition temperature, Tm, was unchanged, but additional phase transitions appeared above Tm. oRTD-1 induced similar effects. However, the effects were not observable below a peptide:lipid molar ratio of 1:50, which correlates with the weaker biological activity of oRTD-1. Small- and wide-angle X-ray scattering revealed for DPPG the appearance of additional structural features induced by RTD-1 above Tm, which were interpreted as correlated lamellar structures, with increased order of the fatty acyl side chains of the lipid. It is proposed that after initial electrostatic interaction of the cationic rim of the peptide with the anionic DPPG headgroups, leading to stabilized lipid-peptide clusters, the hydrophobic face of the peptide assists in its interaction with the fatty acyl side chains eventually leading to membrane disruption.
Abuja
Peter M
PM
Institute of Biophysics and X-Ray Structure Research, Austrian Academy of Sciences, Schmiedlstrasse 6, A-8042 Graz, Austria.
Zenz
Alexandra
A
Trabi
Manuela
M
Craik
David J
DJ
Lohner
Karl
K
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D023082:Defensins / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008567:Membranes, Artificial; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
D000900:Anti-Bacterial Agents; D023082:Defensins; D008081:Liposomes; D008567:Membranes, Artificial; D010456:Peptides, Cyclic; D010715:Phosphatidylglycerols; D015060:1,2-Dipalmitoylphosphatidylcholine; C030345:1,2-dipalmitoylphosphatidylglycerol