Journal
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
Volume 43, Issue 10-11, Pages 499-507Publisher
SPRINGER
DOI: 10.1007/s00249-014-0980-y
Keywords
Peptide-membrane interactions; Membrane topology; Oriented solid-state NMR Spectroscopy; Oriented synchrotron radiation circular dichroism (oSRCD) spectroscopy; Transmembrane helix; In-plane alignment
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Funding
- European Commission [MCRTN-33439]
- Agence Nationale de la Recherche
- University of Strasbourg
- CNRS
- Region Alsace
- RTRA International Center of Frontier Research in Chemistry
- French Foundation for Medical Research (FRM)
- UK Biotechnology and Biological Sciences Research Council
- ISA (Aarhus, Denmark) Synchrotron
- EU Integrated Infrastructure Initiative (I3), European Light Sources Activities (ELISA) [226716]
- BBSRC [BB/J019135/1, BB/H023852/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J019135/1, BB/H023852/1] Funding Source: researchfish
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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.
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