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

作者：Kouno Takahide; Fujitani Naoki; Mizuguchi Mineyuki^*; Osaki Tsukasa; Nishimura Shin ichiro; Kawabata Shun ichiro; Aizawa Tomoyasu; Demura Makoto; Nitta Katsutoshi; Kawan Keiichi

来源：Biochemistry, 2008, 47(40): 10611-10619.

DOI：10.1021/bi800957n

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 P-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 beta-defensins to suppress the growth of Gram-positive bacteria.

• 出版日期2008-10-7