Lipid clustering by three homologous arginine-rich antimicrobial peptides is insensitive to amino acid arrangement and induced secondary structure

Richard M. Epand, Raquel F. Epand, Christopher J. Arnusch, Brigitte Papahadjopoulos-Sternberg, Guangshun Wang, Yechiel Shai

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Three Arg-rich nonapeptides, containing the same amino acid composition but different sequences, PFWRIRIRR-amide (PR-9), RRPFWIIRR-amide (RR-9) and PRFRWRIRI-amide (PI-9), are able to induce segregation of anionic lipids from zwitterionic lipids, as shown by changes in the phase transition properties of lipid mixtures detected by differential scanning calorimetry and freeze fracture electron microscopy. The relative Minimal Inhibitory Concentration (MIC) of these three peptides against several strains of Gram positive bacteria correlated well with the extent to which the lipid composition of the bacterial membrane facilitated peptide-induced clustering of anionic lipids. The lower activity of these three peptides against Gram negative bacteria could be explained by the retention of these peptides in the LPS layer. The membrane morphologies produced by PR-9 as well as by a cathelicidin fragment, KR-12 that had previously been shown to induce anionic lipid clustering, was directly visualized using freeze fracture electron microscopy. This work shows the insensitivity of phase segregation to the specific arrangement of the cationic charges in the peptide sequence as well as to their tendency to form different secondary structures. It also establishes the role of anionic lipid clustering in the presence of zwitterionic lipids in determining antimicrobial selectivity.

Original languageEnglish (US)
Pages (from-to)1272-1280
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1798
Issue number6
DOIs
StatePublished - Jun 1 2010

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Cluster Analysis
Arginine
Lipids
Amino Acids
Peptides
Amides
Electron microscopy
Electron Microscopy
Bacteria
Membranes
Phase Transition
Differential Scanning Calorimetry
Gram-Positive Bacteria
Gram-Negative Bacteria
Chemical analysis
Differential scanning calorimetry
Phase transitions

Keywords

  • Antibacterial peptides
  • Bacterial species specificity
  • Differential scanning calorimetry
  • Freeze fracture electron microscopy
  • Lipid clustering
  • Membrane domains

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Lipid clustering by three homologous arginine-rich antimicrobial peptides is insensitive to amino acid arrangement and induced secondary structure. / Epand, Richard M.; Epand, Raquel F.; Arnusch, Christopher J.; Papahadjopoulos-Sternberg, Brigitte; Wang, Guangshun; Shai, Yechiel.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1798, No. 6, 01.06.2010, p. 1272-1280.

Research output: Contribution to journalArticle

Epand, Richard M. ; Epand, Raquel F. ; Arnusch, Christopher J. ; Papahadjopoulos-Sternberg, Brigitte ; Wang, Guangshun ; Shai, Yechiel. / Lipid clustering by three homologous arginine-rich antimicrobial peptides is insensitive to amino acid arrangement and induced secondary structure. In: Biochimica et Biophysica Acta - Biomembranes. 2010 ; Vol. 1798, No. 6. pp. 1272-1280.
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