Aurein 2.3 functionality is supported by oblique orientated α-helical formation

Mura, Manuela, Dennison, Sarah R., Zvelindovsky, Andrei and Phoenix, David A. (2013) Aurein 2.3 functionality is supported by oblique orientated α-helical formation. Biochimica et Biophysica Acta - Biomembranes, 1828 (2). pp. 586-594. ISSN 0005-2736

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Aurein 2.3 functionality is supported by oblique orientated α-helical formation

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Abstract

In this study, an amphibian antimicrobial peptide, aurein 2.3, was predicted to use oblique orientated α-helix formation in its mechanism of membrane destabilisation. Molecular dynamic (MD) simulations and circular dichroism (CD) experimental data suggested that aurein 2.3 exists in solution as unstructured monomers and folds to form predominantly α-helical structures in the presence of a dimyristoylphosphatidylcholine membrane. MD showed that the peptide was highly surface active, which supported monolayer data where the peptide induced surface pressure changes > 34 mN m - 1. In the presence of a lipid membrane MD simulations suggested that under hydrophobic mismatch the peptide is seen to insert via oblique orientation with a phenylalanine residue (PHE3) playing a key role in the membrane interaction. There is evidence of snorkelling leucine residues leading to further membrane disruption and supporting the high level of lysis observed using calcein release assays (76%). Simulations performed at higher peptide/lipid ratio show peptide cooperativity is key to increased efficiency leading to pore-formation. © 2012 Elsevier B.V. All rights reserved.

Keywords:aurein 2.3, calcein, dimyristoylphosphatidylcholine, leucine, monomer, phenylalanine, polypeptide antibiotic agent, unclassified drug, water, alpha helix, article, circular dichroism, lipid membrane, membrane binding, membrane damage, membrane permeability, molecular dynamics, pressure, priority journal, surface property, Anti-Infective Agents, Antimicrobial Cationic Peptides, Biophysics, Cell Membrane, Computer Simulation, Fluoresceins, Lipids, Models, Molecular, Molecular Conformation, Molecular Dynamics Simulation, Peptides, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Surface Properties, Time Factors, Amphibia
Subjects:C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Mathematics and Physics
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ID Code:14910
Deposited On:11 Sep 2014 11:56

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