The role of C-terminal amidation in the membrane interactions of the anionic antimicrobial peptide, maximin H5

Dennison, Sarah R., Mura, Manuela, Harris, Frederick , Morton, Leslie H. G., Zvelindovsky, Andrei and Phoenix, David A. (2015) The role of C-terminal amidation in the membrane interactions of the anionic antimicrobial peptide, maximin H5. Biochimica et Biophysica Acta - Biomembranes, 1848 (5). pp. 1111-1118. ISSN 0005-2736

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The role of C-terminal amidation in the membrane interactions of the anionic antimicrobial peptide, maximin H5

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Abstract

Maximin H5 is an anionic antimicrobial peptide from amphibians, which carries a C-terminal amide moiety, and was found to be moderately haemolytic (20%). The α-helicity of the peptide was 42% in the presence of lipid mimics of erythrocyte membranes and was found able to penetrate (10.8 mN m- 1) and lyse these model membranes (64 %). In contrast, the deaminated peptide exhibited lower levels of haemolysis (12%) and α-helicity (16%) along with a reduced ability to penetrate (7.8 mN m- 1) and lyse (55%) lipid mimics of erythrocyte membranes. Taken with molecular dynamic simulations and theoretical analysis, these data suggest that native maximin H5 primarily exerts its haemolytic action via the formation of an oblique orientated α-helical structure and tilted membrane insertion. However, the C-terminal deamination of maximin H5 induces a loss of tilted α-helical structure, which abolishes the ability of the peptide's N-terminal and C-terminal regions to H-bond and leads to a loss in haemolytic ability. Taken in combination, these observations strongly suggest that the C-terminal amide moiety carried by maximin H5 is required to stabilise the adoption of membrane interactive tilted structure by the peptide. Consistent with previous reports, these data show that the efficacy of interaction and specificity of maximin H5 for membranes can be attenuated by sequence modification and may assist in the development of variants of the peptide with the potential to serve as anti-infectives.

Keywords:Anionic antimicrobial peptide, ?-Helical, Haemolysis, Lipid monolayer, Lysis, bmjgoldcheck, NotOAChecked
Subjects:C Biological Sciences > C790 Molecular Biology, Biophysics and Biochemistry not elsewhere classified
Divisions:College of Science > School of Mathematics and Physics
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ID Code:16878
Deposited On:27 Mar 2015 11:21

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