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Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/57828

Type: Journal article
Title: Solution structure and membrane interactions of the antimicrobial peptide Fallaxidin 4.1a: An NMR and QCM study
Author: Sherman, P.
Jackway, R.
Gehman, J.
Praporski, S.
McCubbin, G.
Mechler, A.
Martin, L.
Separovic, F.
Bowie, J.
Citation: Biochemistry, 2009; 48(50):11892-11901
Publisher: Amer Chemical Soc
Issue Date: 2009
ISSN: 0006-2960
1520-4995
Statement of
Responsibility: 
Patrick J. Sherman, Rebecca J. Jackway, John D. Gehman, Slavica Praporski, George A. McCubbin, Adam Mechler, Lisandra L. Martin, Frances Separovic and John H. Bowie
Abstract: The solution structure of fallaxidin 4.1a, a C-terminal amidated analogue of fallaxidin 4.1, a cationic antimicrobial peptide isolated from the amphibian Litoria fallax, has been determined by nuclear magnetic resonance (NMR). In zwitterionic dodecylphosphocholine (DPC) micelles, fallaxidin 4.1a adopted a partially helical structure with random coil characteristics. The flexibility of the structure may enhance the binding and penetration upon interaction with microbial membranes. Solid-state (31)P and (2)H NMR was used to investigate the effects of fallaxidin 4.1a on the dynamics of phospholipid membranes, using acyl chain deuterated zwitterionic dimyristoylphosphatidylcholine (DMPC-d(54)) and anionic dimyristoylphosphatidylglycerol (DMPG) multilamellar vesicles. In DMPC-d(54) vesicle bilayers, fallaxidin 4.1a caused a decrease in the (31)P chemical shift anisotropy (CSA), and a decrease in deuterium order parameters from the upper acyl chain region, indicating increased lipid motion about the phosphate headgroups. Conversely, for DMPC-d(54)/DMPG, two (31)P CSA were observed due to a lateral phase separation of the two lipids and/or differing headgroup orientations in the presence of fallaxidin 4.1a, with a preferential interaction with DMPG. Little effect on the deuterated acyl chain order parameters was observed in the d(54)-DMPC/DMPG model membranes. Real time quartz crystal microbalance analyses of fallaxidin 4.1a addition to DMPC and DMPC/DMPG supported lipid bilayers together with the NMR results indicated transmembrane pore formation in DMPC/DMPG membranes and peptide insertion followed by disruption at a threshold concentration in DMPC membranes. The different interactions observed with "mammalian" (DMPC) and "bacterial" (DMPC/DMPG) model membranes imply fallaxidin 4.1a may be a useful antimicrobial peptide, with preferential cytolytic activity toward prokaryotic organisms at low peptide concentrations (<5 microM).
Keywords: Cell Membrane; Animals; Anura; Gram-Positive Bacteria; Quartz; Lipid Bilayers; Dimyristoylphosphatidylcholine; Antimicrobial Cationic Peptides; Solutions; Crystallization; Nuclear Magnetic Resonance, Biomolecular; Amino Acid Sequence; Molecular Sequence Data
Description: Copyright © 2009 American Chemical Society
RMID: 0020094315
DOI: 10.1021/bi901668y
Appears in Collections:Biochemistry publications
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