Structure and mechanism of beta-hairpin antimicrobial peptides in lipid bilayers from solid-state NMR spectroscopy

Mol Biosyst. 2009 Apr;5(4):317-22. doi: 10.1039/b820398a. Epub 2009 Jan 27.


The membrane-bound structure, lipid interaction, and dynamics of the arginine-rich beta-hairpin antimicrobial peptide PG-1 as studied by solid-state NMR are highlighted here. A variety of solid-state NMR techniques, including paramagnetic relaxation enhancement, (1)H and (19)F spin diffusion, dipolar recoupling distance experiments, and 2D anisotropic-isotropic correlation experiments, are used to elucidate the structural basis for the membrane disruptive activity of this representative beta-hairpin antimicrobial peptide. We found that PG-1 structure is membrane dependent: in bacteria-mimetic anionic lipid membranes the peptide forms oligomeric transmembrane beta-barrels, whereas in cholesterol-rich membranes mimicking eukaryotic cells the peptide forms beta-sheet aggregates on the surface of the bilayer. PG-1 causes toroidal pore defects in the anionic membrane, suggesting that the cationic arginine residues drag the lipid phosphate groups along as the peptide inserts. Mutation of PG-1 to reduce the number of cationic residues or to change the arginine guanidinium structure significantly changes the degree of insertion and orientation of the peptide in the lipid membrane, resulting in much weaker antimicrobial activities.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimicrobial Cationic Peptides / chemistry*
  • Humans
  • Lipid Bilayers / chemistry*
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Protein Conformation
  • Structure-Activity Relationship


  • Antimicrobial Cationic Peptides
  • Lipid Bilayers