Dermaseptin S9, an -Helical Antimicrobial Peptide with a Hydrophobic Core and Cationic Termini

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• 作者：Olivier Lequin ; Ali Ladram ; Ludovic Chabbert ; Francine Bruston ; Odile Convert ; Damien Vanhoye ; Gé ; rard Chassaing ; Pierre Nicolas ; and Mohamed Amiche
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：January 17, 2006
• 年：2006
• 卷：45
• 期：2
• 页码：468 - 480
• 全文大小：572K
• 年卷期：v.45,no.2(January 17, 2006)
• ISSN：1520-4995

文摘

The dermaseptins S are closely related peptides with broad-spectrum antibacterial activitythat are produced by the skin of the South American hylid frog, Phyllomedusa sauvagei. These peptidesare polycationic (Lys-rich), -helical, and amphipathic, with their polar/charged and apolar amino acidson opposing faces along the long axis of the helix cylinder. The amphipathic -helical structure is believedto enable the peptides to interact with membrane bilayers, leading to permeation and disruption of thetarget cell. We have identified new members of the dermaseptin S family that do not resemble any of thenaturally occurring antimicrobial peptides characterized to date. One of these peptides, designateddermaseptin S9, GLRSKIWLWVLLMIWQESNKFKKM, has a tripartite structure that includes ahydrophobic core sequence encompassing residues 6-15 (mean hydrophobicity, +4.40, determined bythe Liu-Deber scale) flanked at both termini by cationic and polar residues. This structure is reminiscentof that of synthetic peptides originally designed as transmembrane mimetic models and that spontaneouslybecome inserted into membranes [Liu, L., and Deber, C. M. (1998) Biopolymers 47, 41-62]. DermaseptinS9 is a potent antibacterial, acting on Gram-positive and Gram-negative bacteria. The structure ofdermaseptin S9 in aqueous solution and in TFE/water mixtures was analyzed by circular dichroism andtwo-dimensional NMR spectroscopy combined with molecular dynamics calculations. Dermaseptin S9 isaggregated in water, but a monomeric nonamphipathic -helical conformation, mostly in residues 6-21,is stabilized by the addition of TFE. These results, combined with membrane permeabilization assays andsurface plasmon resonance analysis of the peptide binding to zwitterionic and anionic phospholipid bilayers,demonstrate that spatial segregation of hydrophobic and hydrophilic/charged residues on opposing facesalong the long axis of a helix is not essential for the antimicrobial activity of cationic -helical peptides.