Probing membrane topology of the antimicrobial peptide distinctin by solid-state NMR spectroscopy in zwitterionic and charged lipid bilayers

Raffaello Verardi, Nathaniel Traaseth, Lei Shi, Fernando Porcelli, Luca Monfregola, Stefania De Luca, Pietro Amodeo, Gianluigi Veglia, Andrea Scaloni

Research output: Contribution to journalArticle

Abstract

Distinctin is a 47-residue antimicrobial peptide, which interacts with negatively charged membranes and is active against Gram-positive and Gram-negative bacteria. Its primary sequence comprises two linear chains of 22 (chain 1) and 25 (chain 2) residues, linked by a disulfide bridge between Cys19 of chain 1 and Cys23 of chain 2. Unlike other antimicrobial peptides, distinctin in the absence of the lipid membrane has a well-defined three-dimensional structure, which protects it from protease degradation. Here, we used static solid-state NMR spectroscopy in mechanically aligned lipid bilayers (charged or zwitterionic) to study the topology of distinctin in lipid bilayers. We found that this heterodimeric peptide adopts an ordered conformation absorbed on the surface of the membrane, with the long helix (chain 2), approximately parallel to the lipid bilayer (~ 5° from the membrane plane) and the short helix (chain 1) forming a ~ 24° angle with respect to the bilayer plane. Since the peptide does not disrupt the macroscopic alignment of charged or zwitterionic lipid bilayers at lipid-to-protein molar ratio of 50:1, it is possible that higher peptide concentrations might be needed for pore formation, or alternatively, distinctin elicits its cell disruption action by another mechanism.

Original languageEnglish (US)
Pages (from-to)34-40
Number of pages7
JournalBBA - Biomembranes
Volume1808
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Lipid bilayers
Lipid Bilayers
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Topology
Membranes
Peptides
Membrane Lipids
Gram-Negative Bacteria
Disulfides
Conformations
Bacteria
Peptide Hydrolases
distinctin
Lipids
Degradation
Proteins

Keywords

  • Antimicrobial Peptides
  • Distinctin
  • Mechanically Aligned Bilayer
  • Membrane Protein Topology
  • Oriented Solid-State NMR

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

Cite this

Probing membrane topology of the antimicrobial peptide distinctin by solid-state NMR spectroscopy in zwitterionic and charged lipid bilayers. / Verardi, Raffaello; Traaseth, Nathaniel; Shi, Lei; Porcelli, Fernando; Monfregola, Luca; De Luca, Stefania; Amodeo, Pietro; Veglia, Gianluigi; Scaloni, Andrea.

In: BBA - Biomembranes, Vol. 1808, No. 1, 01.2011, p. 34-40.

Research output: Contribution to journalArticle

Verardi, Raffaello ; Traaseth, Nathaniel ; Shi, Lei ; Porcelli, Fernando ; Monfregola, Luca ; De Luca, Stefania ; Amodeo, Pietro ; Veglia, Gianluigi ; Scaloni, Andrea. / Probing membrane topology of the antimicrobial peptide distinctin by solid-state NMR spectroscopy in zwitterionic and charged lipid bilayers. In: BBA - Biomembranes. 2011 ; Vol. 1808, No. 1. pp. 34-40.
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