A novel β-defensin structure: A potential strategy of big defensin for overcoming resistance by gram-positive bacteria

Takahide Kouno, Naoki Fujitani, Mineyuki Mizuguchi, Tsukasa Osaki, Shin Ichiro Nishimura, Shun-Ichiro Kawabata, Tomoyasu Aizawa, Makoto Demura, Katsutoshi Nitta, Keiichi Kawano

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26 Citations (Scopus)

Abstract

Big defensin is a 79-residue peptide derived from hemocytes of the Japanese horseshoe crab. It has antimicrobial activities against Gram-positive and -negative bacteria. The amino acid sequence of big defensin can be divided into an N-terminal hydrophobic half and a C-terminal cationic half. Interestingly, the trypsin cleaves big defensin into two fragments, the N-terminal and C-terminal fragments, which are responsible for antimicrobial activity against Gram-positive and -negative bacteria, respectively. To explore the antimicrobial mechanism of big defensin, we determined the solution structure of mature big defensin and performed a titration experiment with DPC micelles. Big defensin has a novel defensin structure; the C-terminal domain adopts a β-defensin structure, and the N-terminal domain forms a unique globular conformation. It is noteworthy that the hydrophobic N-terminal domain undergoes a conformational change in micelle solution, while the C-terminal domain remains unchanged. Here, we propose that the N-terminal domain achieves its antimicrobial activity in a novel fashion and explain that big defensin has developed a sttategy different from those of other β-defensins to suppress the growth of Gram-positive bacteria.

Original languageEnglish
Pages (from-to)10611-10619
Number of pages9
JournalBiochemistry
Volume47
Issue number40
DOIs
Publication statusPublished - Oct 7 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Kouno, T., Fujitani, N., Mizuguchi, M., Osaki, T., Nishimura, S. I., Kawabata, S-I., Aizawa, T., Demura, M., Nitta, K., & Kawano, K. (2008). A novel β-defensin structure: A potential strategy of big defensin for overcoming resistance by gram-positive bacteria. Biochemistry, 47(40), 10611-10619. https://doi.org/10.1021/bi800957n