Perrone, B. and Miles, Andrew J. and Salnikov, E.S. and Wallace, Bonnie A. and Bechinger, B. (2014) Lipid interactions of LAH4, a peptide with antimicrobial and nucleic acid transfection activities. European Biophysics Journal with Biophysics letters 43 (10-11), pp. 499-507. ISSN 0175-7571.
Abstract
The cationic amphipathic designer peptide LAH4 exhibits potent antimicrobial, nucleic acid transfection and cell penetration activities. Closely related derivatives have been developed to enhance viral transduction for gene therapeutic assays. LAH4 contains four histidines and, consequently, its overall charge and membrane topology in lipid bilayers are strongly pH dependent. In order to better understand the differential interactions of this amphipathic peptide with negatively-charged membranes its interactions, topologies, and penetration depth were investigated in the presence of lipid bilayers as a function of pH, buffer, phospholipid head group, and fatty acyl chain composition using a combination of oriented synchrotron radiation circular dichroism spectroscopy as well as oriented and non-oriented solid-state NMR spectroscopy. This combination of methods indicates that in the presence of lipids with phosphatidylglycerol head groups, the topological equilibria of LAH4 is shifted towards more in-plane configurations even at neutral pH. In contrast, a transmembrane alignment is promoted when LAH4 interacts with membranes made of dimyristoyl phospholipids rather than palmitoyl-oleoyl-phospholipids. Finally, the addition of citrate buffer favours LAH4 transmembrane alignments, even at low pH, probably by complex formation with the cationic charges of the peptide. In summary, this study has revealed that the membrane topology of this peptide is readily modulated by the environmental conditions.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | Peptide-membrane interactions, Membrane topology, Oriented solid-state NMR Spectroscopy, Oriented synchrotron radiation circular dichroism, (oSRCD) spectroscopy, Transmembrane helix, In-plane alignment |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Bioinformatics, Bloomsbury Centre for (Closed), Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 29 Apr 2015 12:35 |
| Last Modified: | 02 Aug 2023 17:16 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/12002 |
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