Structure and Bacterial Cell Selectivity of a Fish-Derived Antimicrobial Peptide, Pleurocidin

  • Yang Ji-Young (Department of Advanced Fusion Technology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Shin Song-Yub (Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University) ;
  • Lim Shin-Saeng (Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University) ;
  • Hahm Kyung-Soo (Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University) ;
  • Kim Yang-Mee (Department of Advanced Fusion Technology, Bio/Molecular Informatics Center, Konkuk University)
  • 발행 : 2006.06.01

초록

Pleurocidin, an $\alpha$-helical cationic antimicrobial peptide, was isolated from skin mucosa of winter flounder (Pleuronectes americamus). It had strong antimicrobial activities against Gram-positive and Gram-negative bacteria, but had very weak hemolytic activity. The Gly$^{13,17}\rightarrow$Ala analog (pleurocidin-AA) showed similar antibacterial activities, but had dramatically increased hemolytic activity. The bacterial cell selectivity of pleurocidin was confirmed through the membrane-disrupting and membrane-binding affinities using dye leakage, tryptophan fluorescence blue shift, and tryptophan quenching experiments. However, the non-cell-selective antimicrobial peptide, pleurocidin-AA, interacts strongly with both negatively charged and zwitterionic phospholipid membranes, the latter of which are the major constituents of the outer leaflet of erythrocytes. Circular dihroism spectra showed that pleurocidin-AA has much higher contents of $\alpha$-helical conformation than pleurocidin. The tertiary structure determined by NMR spectroscopy showed that pleurocidin has a flexible. structure between the long helix from $Gly^3$ to $Gly^{17}$ and the short helix from $Gly^{17}$ to $Leu^{25}$. Cell-selective antimicrobial peptide pleurocidin interacts strongly with negatively charged phospholipid membranes, which mimic bacterial membranes. Structural flexibility between the two helices may play a key role in bacterial cell selectivity of pleurocidin.

키워드

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