Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/105331
Title: Progressive structuring of a branched antimicrobial peptide on the path to the inner membrane target
Authors: Beuerman, Roger W.
Bai, Yang
Liu, Shouping
Li, Jianguo
Lakshminarayanan, Rajamani
Sarawathi, Padmanabhan
Tang, Charles
Ho, Duncun
Verma, Chandra
Pervushin, Konstantin
Keywords: DRNTU::Science::Biological sciences::Biochemistry
Issue Date: 2012
Source: Bai, Y., Liu, S., Li, J., Lakshminarayanan, R., Sarawathi, P., Tang, C., et al. (2012). Progressive structuring of a branched antimicrobial peptide on the path to the inner membrane target. Journal of biological chemistry, 287(32), 26606-26617.
Series/Report no.: Journal of biological chemistry
Abstract: In recent years, interest has grown in the antimicrobial properties of certain natural and non-natural peptides. The strategy of inserting a covalent branch point in a peptide can improve its antimicrobial properties while retaining host biocompatibility. However, little is known regarding possible structural transitions as the peptide moves on the access path to the presumed target, the inner membrane. Establishing the nature of the interactions with the complex bacterial outer and inner membranes is important for effective peptide design. Structure-activity relationships of an amphiphilic, branched antimicrobial peptide (B2088) are examined using environment-sensitive fluorescent probes, electron microscopy, molecular dynamics simulations, and high resolution NMR in solution and in condensed states. The peptide is reconstituted in bacterial outer membrane lipopolysaccharide extract as well as in a variety of lipid media mimicking the inner membrane of Gram-negative pathogens. Progressive structure accretion is observed for the peptide in water, LPS, and lipid environments. Despite inducing rapid aggregation of bacteria-derived lipopolysaccharides, the peptide remains highly mobile in the aggregated lattice. At the inner membranes, the peptide undergoes further structural compaction mediated by interactions with negatively charged lipids, probably causing redistribution of membrane lipids, which in turn results in increased membrane permeability and bacterial lysis. These findings suggest that peptides possessing both enhanced mobility in the bacterial outer membrane and spatial structure facilitating its interactions with the membrane-water interface may provide excellent structural motifs to develop new antimicrobials that can overcome antibiotic-resistant Gram-negative pathogens.
URI: https://hdl.handle.net/10356/105331
http://hdl.handle.net/10220/17200
DOI: 10.1074/jbc.M112.363259
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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