A novel beta-defensin structure: a potential strategy of big defensin for overcoming resistance by Gram-positive bacteria.
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 beta-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.
Kouno
Takahide
T
Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
Fujitani
Naoki
N
Mizuguchi
Mineyuki
M
Osaki
Tsukasa
T
Nishimura
Shin-ichiro
S
Kawabata
Shun-ichiro
S
Aizawa
Tomoyasu
T
Demura
Makoto
M
Nitta
Katsutoshi
K
Kawano
Keiichi
K
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006434:Hemocytes / Q000378:metabolism; D006737:Horseshoe Crabs / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D023083:beta-Defensins / Q000737:chemistry* / Q000494:pharmacology*
D000890:Anti-Infective Agents; D023083:beta-Defensins