Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling

Sebastien Farnaud, Alpesh Patel, Edward W. Odell, Robert W. Evans

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Antimicrobial peptides bovine lactoferricin (LfcinB) and human lactoferricin (LfcinH) are produced from the respective lactoferrin, but are more active than their precursors. Despite sequence homology, the bovine peptide and its derivatives are more active than their human homologs. Such differences between not only the peptides and their precursor but also between the bovine and the human peptides could relate to structural differences. Upon sequence alignment of both peptides with their parental proteins, the structural differences observed between the bovine lactoferrin (BLf) and LfcinB were also found between the human lactoferrin (HLf) and the LfcinH. The helical structures in HLf are replaced by β-strands separated by a strong turn in LfcinH suggesting an antiparallel β-sheet structure similar to LfcinB. MIC assays with HLP-2 and BLP-2, 11-residue peptides derived from the active core of both Lfcins, against Escherichia coli, showed that the bovine derivative, BLP-2, is more active than its human homolog HLP-2. Both 3D models for HLP-2 and BLP-2 showed that the β-strand is centred between the aromatic residues giving both side chains the same orientations. The displacement towards the N-terminus observed for the β-strand in HLP-2, compared with its central location in BLP-2, could be less favourable to membrane interaction and therefore responsible for the decrease in activity. Such a model suggests for LfcinH a mechanism similar to the one observed for LfcinB, where the absence of long-range interaction, present in lactoferrin, destabilises the first alpha helix, as observed in solution and, upon interaction with the membrane, could result in the formation of a β-strand, as observed in the presence of LPS. The location of the β-strand in relation to the positive charges, seems to define the efficiency of the activity of the peptide and may explain the difference in activity obtained between HLP-2 and BLP-2.

Original languageEnglish
Pages (from-to)221-226
Number of pages6
JournalFEMS Microbiology Letters
Volume238
Issue number1
DOIs
Publication statusPublished - 1 Sep 2004
Externally publishedYes

Fingerprint

Lactoferrin
Peptides
lactoferricin B
Membranes
Sequence Alignment
Sequence Homology
HLP-2 polypeptide
Escherichia coli
Proteins

Keywords

  • Cationic antimicrobial peptides
  • Lactoferricin
  • Lactoferrin
  • LPS
  • Modeller

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Applied Microbiology and Biotechnology
  • Microbiology

Cite this

Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling. / Farnaud, Sebastien; Patel, Alpesh; Odell, Edward W.; Evans, Robert W.

In: FEMS Microbiology Letters, Vol. 238, No. 1, 01.09.2004, p. 221-226.

Research output: Contribution to journalArticle

Farnaud, Sebastien ; Patel, Alpesh ; Odell, Edward W. ; Evans, Robert W. / Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling. In: FEMS Microbiology Letters. 2004 ; Vol. 238, No. 1. pp. 221-226.
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