Membrane interactions of proline-rich antimicrobial peptide, Chex1-Arg20, multimers

Wenyi Li; Marc-Antoine Sani; Elaheh Jamasbi; Laszlo Otvos Jr; Mohammed Akhter Hossain; John D Wade; Frances Separovic

doi:10.1016/j.bbamem.2016.02.035

Membrane interactions of proline-rich antimicrobial peptide, Chex1-Arg20, multimers

Biochim Biophys Acta. 2016 Jun;1858(6):1236-43. doi: 10.1016/j.bbamem.2016.02.035. Epub 2016 Feb 27.

Authors

Wenyi Li¹, Marc-Antoine Sani², Elaheh Jamasbi², Laszlo Otvos Jr³, Mohammed Akhter Hossain¹, John D Wade¹, Frances Separovic⁴

Affiliations

¹ School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC 3010, Australia.
² School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia.
³ Department of Biology, Temple University, Philadelphia, PA 19122, USA; Institute of Medical Microbiology, Semmelweis University, Budapest 1089, Hungary.
⁴ School of Chemistry, Bio21 Institute, University of Melbourne, VIC 3010, Australia. Electronic address: fs@unimelb.edu.au.

PMID: 26926423
DOI: 10.1016/j.bbamem.2016.02.035

Abstract

The increasing prevalence of antibiotic-resistant pathogens requires the development of new antibiotics. Proline-rich antimicrobial peptides (PrAMPs), including native apidaecins, Bac7, and oncocins or designed A3APO, show multi-modal actions against pathogens together with immunostimulatory activities. The interactions of the designed PrAMP, Chex1-Arg20, and its dimeric and tetrameric oligomers with different model membranes were investigated by circular dichroism spectroscopy, dynamic light scattering, zeta potential, differential scanning calorimetry, and dye leakage. Chex1-Arg20 oligomers showed stronger affinity and preferential binding to negatively charged phospholipid bilayers and led to lipid aggregation and neutralization. Fluorescence microscopy of negatively charged giant unilamellar vesicles with AlexFluor-647-labeled Chex1-Arg20 dimers and tetramers displayed aggregation at a peptide/lipid low ratio of 1:200 and at higher peptide concentrations (1:100/1:50) for Chex1-Arg20 monomer. Such interactions, aggregation, and neutralization of PrAMP oligomers additionally showed the importance of interactions of PrAMPs with negatively charged membranes.

Keywords: Chex1-Arg20 multimers; Lipid–peptide interactions; Liposomes; Phospholipid bilayers; Proline-rich antimicrobial peptides.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Anti-Infective Agents / chemistry
Anti-Infective Agents / metabolism*
Biopolymers / metabolism*
Cell Membrane / metabolism
Circular Dichroism
Lipid Bilayers
Membrane Potentials
Microscopy, Fluorescence
Molecular Sequence Data
Peptides / chemistry
Peptides / metabolism*
Protein Binding
Protein Conformation

Substances

Anti-Infective Agents
Biopolymers
Lipid Bilayers
Peptides