期刊
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
卷 1804, 期 4, 页码 806-820出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbapap.2009.12.006
关键词
Novicidin; Membrane permeabilization; Confocal laser scanning microscopy; Circular dichroism; Liquid- and solid-state NMR; Peptide acylation
资金
- Danish National Research Foundation
- Aalborg University
- Villum Kann Rasmussen Foundation
- Obel Foundation
Many small cationic peptides, which are unstructured in aqueous solution, have antimicrobial properties. These properties are assumed to be linked to their ability to permeabilize bacterial membranes, accompanied by the transition to an alpha-helical folding state. Here we show that there is no direct link between folding of the antimicrobial peptide Novicidin (Nc) and its membrane permeabilization. N-terminal acylation with C8-C1 6 alkyl chains and the inclusion of anionic lipids both increase Nc's ability to form alpha-helical structure in the presence of vesicles. Nevertheless, both acylation and anionic lipids reduce the extent of permeabilization of these vesicles and lead to slower permeabilization kinetics. Furthermore, acylation significantly decreases antimicrobial activity. Although acyl chains of increasing length also increase the tendency of the peptides to aggregate in solution, this cannot rationalize our results since permeabilization and antimicrobial activities are observed well below concentrations where aggregation occurs. This suggests that significant induction of alpha-helical structure is not a prerequisite for membrane perturbation in this class of antimicrobial peptides. Our data suggests that for Nc, induction of alpha-helical structure may inhibit rather than facilitate membrane disruption, and that a more peripheral interaction may be the most efficient permeabilization mechanism. Furthermore, acylation leads to a deeper embedding in the membrane, which could lead to an anti-permeabilizing plugging effect. (C) 2009 Elsevier B.V. All rights reserved.
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