Stable isotope-assisted NMR characterization of interaction between lipid A and sarcotoxin IA, a cecropin-type antibacterial peptide
- Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787 (Japan)
- Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan)
- Bioscience Research Laboratory, Fujiya Co., Ltd., Hadano, Kanagawa 257-0031 (Japan)
- Department of Biochemistry and Cell Biology, National Institute of Infectious Disease, Tokyo 162-8640 (Japan)
- National Institute of Agrobiological Sciences, Tsukuba 305-8602 (Japan)
Highlights: ► Recombinant sarcotoxin IA was successfully produced with {sup 13}C- and {sup 15}N-labeling. ► Sarcotoxin IA adopts an N-terminal α-helix upon binding to lipid A-embedding micelles. ► Two lysine residues are involved in lipid A-mediated antibacterial activities. -- Abstract: 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 {sup 13}C- and {sup 15}N-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 α-helix upon its interaction with the aqueous micelles. Furthermore, chemical shift perturbation data indicated that the amino acid residues displayed on this α-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.
- OSTI ID:
- 22224336
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 431, Issue 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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