Dimer structure of magainin 2 bound to phospholipid vesicles

Magainin 2 from African clawed frog Xenopus laevis is an antimicrobial peptide with broad spectra and action mechanisms considered to permeabilize bacterial membranes. CD, vibration, and solid‐state NMR spectroscopies indicate the peptide adopts an α‐helical conformation on binding to phospholipid bilayers, and its micelle‐bound conformation, being monomeric and α‐helical, is well detailed. We showed, however, that the peptide dimerizes on binding to phospholipid bilayers. This difference in the conformation and aggregation state between micelle‐ and bilayer‐bound states prompted us to analyze the conformation of an equipotent analog of magainin 2 (F5Y,F16W magainin 2) bound to phosphatidylcholine vesicles using transferred nuclear Overhauser enhancement (TRNOE) spectroscopy. While observed medium‐range TRNOE cross peaks were characteristic of α‐helix, many long‐range cross peaks were not compatible with the peptide's monomeric state. Simulated annealing calculations generated dimer structures indicating (1) two peptide molecules have a largely helical conformation in antiparallel orientation forming a short coiled‐coil structure, (2) residues 4–20 are well converged and residues 9–20 are in an α‐helical conformation, and (3) the interface of the two peptide molecules is formed by well‐defined side chains of hydrophobic residues. Finally, determined structures are compatible with numerous investigations examining magainin–phospholipid interactions. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 314–327, 2002