Antimicrobial peptide RP-1 structure and interactions with anionic versus zwitterionic micelles

Area of Science:

• Biochemistry
• Structural Biology
• Antimicrobial Peptides

Background:

• Platelet factor-4 kinocidins possess microbicidal activity mediated by their C-terminal alpha-helices.
• The synthetic antimicrobial peptide RP-1 is modeled on these microbicidal domains.

Purpose of the Study:

• To elucidate the high-resolution structure of RP-1 in membrane-mimicking environments.
• To investigate the interaction of RP-1 with anionic and zwitterionic lipid bilayers.
• To assess the utility of molecular dynamics simulations in predicting peptide-micelle interactions.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy in sodium dodecyl sulfate (SDS) and dodecylphosphocholine (DPC) micelles.
• Paramagnetic probe NMR experiments.
• Molecular Dynamics (MD) simulations.

Main Results:

• RP-1 adopts an amphipathic alpha-helical conformation in both SDS and DPC micelles.
• Subtle differences in side-chain orientation and peptide positioning were observed between SDS and DPC.
• MD simulations revealed RP-1 deeply perturbs SDS micelles but interacts peripherally with DPC micelles.
• Experimental and simulation data indicate preferential binding of RP-1 to anionic membranes.

Conclusions:

• RP-1 exhibits specificity for anionic membranes, consistent with prokaryotic cell membranes.
• The peptide's preferential interaction stems from distinct lipid-binding modes rather than major structural alterations.
• This study validates the use of NMR and MD simulations for characterizing antimicrobial peptide-membrane interactions.