A Novel β-Defensin Structure: A Potential Strategy of Big Defensin for Overcoming Resistance by Gram-Positive Bacteria

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• 作者：Takahide Kouno ; Naoki Fujitani ; Mineyuki Mizuguchi ; Tsukasa Osaki ; Shin-ichiro Nishimura ; Shun-ichiro Kawabata ; Tomoyasu Aizawa ; Makoto Demura ; Katsutoshi Nitta ; Keiichi Kawano
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：October 7, 2008
• 年：2008
• 卷：47
• 期：40
• 页码：10611-10619
• 全文大小：412K
• 年卷期：v.47,no.40(October 7, 2008)
• ISSN：1520-4995

文摘

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 strategy different from those of other β-defensins to suppress the growth of Gram-positive bacteria.