Stable isotope-assisted NMR characterization of interaction between lipid A and sarcotoxin IA, a cecropin-type antibacterial peptide

作者：Yagi Utsumi Maho; Yamaguchi Yoshiki; Boonsri Pornthip; Iguchi Takeshi; Okemoto Kazuo; Natori Shunji; Kato Koichi^*

来源：Biochemical and Biophysical Research Communications, 2013, 431(2): 136-140.

DOI：10.1016/j.bbrc.2013.01.009

• NMR
• Lipid A
• Sarcotoxin
• Antimicrobial peptide
• Cecropin
• Micelles

Sarcotoxin IA is a 39-residue cecropin-type peptide from Sarcophaga peregrina. This peptide exhibits antibacterial activity against Gram-negative bacteria through its interaction with lipid A, a core component of lipopolysaccharides. To acquire detailed structural information on this specific interaction, we performed NMR analysis using bacterially expressed sarcotoxin IA analogs with C-13- and N-15-labeling along with lipid A-embedding micelles composed of dodecylphosphocholine. By inspecting the stable isotope-assisted NMR data, we revealed that the N-terminal segment (Leu3-Arg18) of sarcotoxin IA formed an amphiphilic alpha-helix upon its interaction with the aqueous micelles. Furthermore, chemical shift perturbation data indicated that the amino acid residues displayed on this alpha-helix were involved in the specific interaction with lipid A. On the basis of these data, we successfully identified Lys4 and Lys5 as key residues in the interaction with lipid A and the consequent antibacterial activity. Therefore, these results provide unique information for designing chemotherapeutics based on antibacterial peptide structures.

• 出版日期2013-2-8