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Solution structure and membrane interactions of the antimicrobial peptide fallaxidin 4.1a: an NMR and QCM study.

Authors :
Sherman PJ
Jackway RJ
Gehman JD
Praporski S
McCubbin GA
Mechler A
Martin LL
Separovic F
Bowie JH
Source :
Biochemistry [Biochemistry] 2009 Dec 22; Vol. 48 (50), pp. 11892-901.
Publication Year :
2009

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).

Details

Language :
English
ISSN :
1520-4995
Volume :
48
Issue :
50
Database :
MEDLINE
Journal :
Biochemistry
Publication Type :
Academic Journal
Accession number :
19894755
Full Text :
https://doi.org/10.1021/bi901668y