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 alpha-helical conformation on binding to phospholipid bilayers, and its micelle-bound conformation, being monomeric and alpha-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 alpha-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 alpha-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.
Wakamatsu
Kaori
K
Department of Biochemical Sciences, Faculty of Engineering, Gunma University, Kiryu, Gunma 376-8515, Japan. wakamats@bce.gunma-u.ac.jp
Takeda
Akemi
A
Tachi
Tomoya
T
Matsuzaki
Katsumi
K
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D019295:Computational Biology; D019281:Dimerization; D054806:Magainins; D009682:Magnetic Resonance Spectroscopy; D010743:Phospholipids / Q000737:chemistry*; D029867:Xenopus Proteins; D014982:Xenopus laevis
D023181:Antimicrobial Cationic Peptides; D054806:Magainins; D010743:Phospholipids; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus