Molecular insight into mechanism of antimicrobial action of the beta-hairpin peptide arenicin: specific oligomerization in detergent micelles

Biopolymers. 2008 May;89(5):455-64. doi: 10.1002/bip.20865.

Abstract

Arenicins are 21-residue cationic antimicrobial peptides isolated from marine polychaeta Arenicola marina. The peptides exhibit potent broad-spectrum antimicrobial activity. In water solution arenicin-2 adopts a beta-hairpin conformation, stabilized by one disulfide and nine hydrogen bonds. To determine the propensity for the peptide oligomerization in membrane mimetic systems, the recombinant arenicin-2 was overexpressed as a fused form in Escherichia coli. The arenicin-2 oligomerization and intermolecular packing in membrane mimicking environment were investigated using high-resolution NMR spectroscopy. The present studies show that arenicin-2 preserves a beta-hairpin structure and forms asymmetric dimers upon incorporation into the dodecylphosphocholine micelle. Two monomers of arenicin-2 are aligned parallel to each other by the N-terminal strands of the beta-hairpin (CN upward arrow upward arrowNC type of association). Polyacrylamide gel electrophoresis analysis indicated that in environment of anionic SDS micelles the arenicin-2 might undergo further oligomerization and form tetramers. Our results afford further molecular insight into possible mechanism of antimicrobial action of arenicins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / isolation & purification
  • Detergents / chemistry*
  • Detergents / pharmacology
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • Helminth Proteins
  • Magnetic Resonance Spectroscopy
  • Micelles*
  • Peptides / chemistry*
  • Peptides / isolation & purification
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / chemistry
  • Protein Structure, Secondary
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antimicrobial Cationic Peptides
  • Detergents
  • Helminth Proteins
  • Micelles
  • Peptides
  • arenicin-1, Arenicola marina
  • Phosphorylcholine
  • dodecylphosphocholine