| Title: | Proline-15 creates an amphipathic wedge in maculatin 1.1 peptides that drives lipid membrane disruption |
| Author(s): | Sani MA; Lee TH; Aguilar MI; Separovic F; |
| Address: | "School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. Electronic address: mibel.aguilar@monash.edu. School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia. Electronic address: fs@unimelb.edu.au" |
| DOI: | 10.1016/j.bbamem.2015.06.013 |
| ISSN/ISBN: | 0006-3002 (Print) 0006-3002 (Linking) |
| Abstract: | "The membrane interaction of peptides derived from maculatin 1.1 and caerin 1.1, with the sequence motif of N and C termini of maculatin 1.1, was compared in order to understand the role of these common sequence motifs, which encompass critical proline residues, on peptide secondary structure and on membrane binding and disruption in zwitterionic and anionic membranes. The peptides incorporated a single substitution with lysine or deletion of the central region to mimic the length of the antimicrobial peptides, citropin 1.1 and aurein 1.2. The impact of these changes in the sequence, length and physicochemical properties, on lytic activity and structure was assessed by dye-release from lipid vesicles and the change in the bilayer order as a function of membrane-bound peptide mass. All peptides adopted similar degrees of helical structure in both membrane systems. In addition, all peptide analogues were less active than either maculatin 1.1 or caerin 1.1 in dye release assays. The membrane binding was analyzed by dual polarization interferometry and the results showed that membrane binding was significantly affected by changes in the hydrophobic environment of Pro-15. Moreover, changes in the relative distribution of charge and hydrophobicity flanking Pro-15 also caused significant changes to the membrane order. Overall, the proline residue plays an important role in inducing a peptide structure that enhances the activity of these antimicrobial peptides" |
| Keywords: | "Amphibian Proteins/*chemistry/*ultrastructure Antimicrobial Cationic Peptides/*chemistry Binding Sites Computer Simulation Lipid Bilayers/*chemistry *Membrane Fluidity Models, Chemical Models, Molecular Permeability Proline/*chemistry Protein Binding Prot;" |
| Notes: | "MedlineSani, Marc-Antoine Lee, Tzong-Hsien Aguilar, Marie-Isabel Separovic, Frances eng Comparative Study Research Support, Non-U.S. Gov't Netherlands 2015/06/17 Biochim Biophys Acta. 2015 Oct; 1848(10 Pt A):2277-89. doi: 10.1016/j.bbamem.2015.06.013. Epub 2015 Jun 14" |
