An acidic model pro-peptide affects the secondary structure, membrane interactions and antimicrobial activity of a crotalicidin fragment

Sci Rep. 2018 Jul 24;8(1):11127. doi: 10.1038/s41598-018-29444-0.

Abstract

In order to study how acidic pro-peptides inhibit the antimicrobial activity of antimicrobial peptides, we introduce a simple model system, consisting of a 19 amino-acid long antimicrobial peptide, and an N-terminally attached, 10 amino-acid long acidic model pro-peptide. The antimicrobial peptide is a fragment of the crotalicidin peptide, a member of the cathelidin family, from rattlesnake venom. The model pro-peptide is a deca (glutamic acid). Attachment of the model pro-peptide only leads to a moderately large reduction in the binding to- and induced leakage of model liposomes, while the antimicrobial activity of the crotalicidin fragment is completely inhibited by attaching the model pro-peptide. Attaching the pro-peptide induces a conformational change to a more helical conformation, while there are no signs of intra- or intermolecular peptide complexation. We conclude that inhibition of antimicrobial activity by the model pro-peptide might be related to a conformational change induced by the pro-peptide domain, and that additional effects beyond induced changes in membrane activity must also be involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / pharmacology
  • Crotalid Venoms / chemistry*
  • Crotalid Venoms / genetics
  • Crotalus / genetics
  • Escherichia coli / drug effects
  • Escherichia coli / pathogenicity
  • Glutamic Acid / chemistry
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / pathogenicity
  • Liposomes / antagonists & inhibitors
  • Liposomes / chemistry
  • Membranes / drug effects
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology
  • Protein Conformation / drug effects
  • Protein Structure, Secondary / drug effects
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / pathogenicity

Substances

  • Antimicrobial Cationic Peptides
  • Crotalid Venoms
  • Liposomes
  • Peptide Fragments
  • crotalicidin
  • Glutamic Acid