title: A novel beta-defensin structure: big defensin changes its N-terminal structure to associate with the target membrane.
abstract: Big defensin is a 79-residue peptide derived from hemocytes of the Japanese horseshoe crab. The amino acid sequence of big defensin is divided into an N-terminal hydrophobic domain and a C-terminal cationic domain, which are responsible for antimicrobial activities against Gram-positive and -negative bacteria, respectively. The N-terminal domain of big defensin forms a unique globular conformation with two alpha-helices and a parallel beta-sheet, while the C-terminal domain adopts a beta-defensin-like fold. Although our previous study implied that big defensin changes its N-terminal structure in a micellar environment, due to the poor quality of the NMR spectra it remained to be resolved whether the N-terminal domain adopts any structure in the presence of micelles. In this analysis, we successfully determined the structure of the N-terminal fragment of big defensin in a micellar solution, showing that the fragment peptide forms a single alpha-helix structure. Moreover, NMR experiments using paramagnetic probes revealed that the N-terminal domain of big defensin penetrates into the micelle with a dipping at the N-terminal edge of the alpha-helix. Here, we propose a model for how big defensin associates with the target membrane.
authors: Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors: Takahide
authors: T
authors: Kouno
authors: Mineyuki
authors: M
authors: Mizuguchi
authors: Tomoyasu
authors: T
authors: Aizawa
authors: Hiroyuki
authors: H
authors: Shinoda
authors: Makoto
authors: M
authors: Demura
authors: Shun-ichiro
authors: S
authors: Kawabata
authors: Keiichi
authors: K
authors: Kawano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D023083:beta-Defensins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D010455:Peptides; D023083:beta-Defensins