Dynamic Structure and Orientation of Melittin Bound to Acidic Lipid Bilayers, As Revealed by Solid-State NMR and Molecular Dynamics Simulation.
Melittin is a venom peptide that disrupts lipid bilayers at temperatures below the liquid-crystalline to gel phase transition temperature (Tc). Notably, the ability of melittin to disrupt acidic dimyristoylphosphatidylglycerol (DMPG) bilayers was weaker than its ability to disrupt neutral dimyristoylphosphatidylcholine bilayers. The structure and orientation of melittin bound to DMPG bilayers were revealed by analyzing the13C chemical shift anisotropy of [1-13C]-labeled melittin obtained from solid-state13C NMR spectra.13C chemical shift anisotropy showed oscillatory shifts with the index number of residues. Analysis of the chemical shift oscillation properties indicated that melittin bound to a DMPG membrane adopts a bent α-helical structure with tilt angles for the N- and C-terminal helices of -32 and +30°, respectively. The transmembrane melittin in DMPG bilayers indicates that the peptide protrudes toward the C-terminal direction from the core region of the lipid bilayer to show a pseudotransmembrane bent α-helix. Molecular dynamics simulation was performed to characterize the structure and interaction of melittin with lipid molecules in DMPG bilayers. The simulation results indicate that basic amino acid residues in melittin interact strongly with lipid head groups to generate a pseudo-transmembrane alignment. The N-terminus is located within the lipid core region and disturbs the lower surface of the lipid bilayer.
Graduate School of Engineering, Yokohama National University , 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
Kazushi
K
Norisada
Graduate School of Engineering, Yokohama National University , 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.|School of Engineering and Applied Sciences, National University of Mongolia , Ulaanbaatar 14201, Mongolia.
Namsrai
N
Javkhlantugs
Graduate School of Engineering, Yokohama National University , 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
Daisuke
D
Mishima
Graduate School of Engineering, Yokohama National University , 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
Izuru
0000-0002-8163-9695
I
Kawamura
Department of Life Science, University of Hyogo , Harima Science Garden City, Kamigori, Hyogo 678-1297, Japan.
Hazime
H
Saitô
Graduate School of Engineering, Yokohama National University , 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
Kazuyoshi
K
Ueda
Graduate School of Engineering, Yokohama National University , 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan.
Akira
0000-0003-2443-6135
A
Naito
D000595:Amino Acid Sequence; D000818:Animals; D016880:Anisotropy; D001516:Bees / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010715:Phosphatidylglycerols / Q000737:chemistry*; D017433:Protein Structure, Secondary
D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; D008555:Melitten; C002773:dimyristoylphosphatidylglycerol