Micelle-Triggered β-Hairpin to α-Helix Transition in a 14-Residue Peptide from a Choline-Binding Repeat of the Pneumococcal Autolysin LytA

Chemistry. 2015 May 26;21(22):8076-89. doi: 10.1002/chem.201500447. Epub 2015 Apr 27.

Abstract

Choline-binding modules (CBMs) have a ββ-solenoid structure composed of choline-binding repeats (CBR), which consist of a β-hairpin followed by a short linker. To find minimal peptides that are able to maintain the CBR native structure and to evaluate their remaining choline-binding ability, we have analysed the third β-hairpin of the CBM from the pneumococcal LytA autolysin. Circular dichroism and NMR data reveal that this peptide forms a highly stable native-like β-hairpin both in aqueous solution and in the presence of trifluoroethanol, but, strikingly, the peptide structure is a stable amphipathic α-helix in both zwitterionic (dodecylphosphocholine) and anionic (sodium dodecylsulfate) detergent micelles, as well as in small unilamellar vesicles. This β-hairpin to α-helix conversion is reversible. Given that the β-hairpin and α-helix differ greatly in the distribution of hydrophobic and hydrophilic side chains, we propose that the amphipathicity is a requirement for a peptide structure to interact and to be stable in micelles or lipid vesicles. To our knowledge, this "chameleonic" behaviour is the only described case of a micelle-induced structural transition between two ordered peptide structures.

Keywords: micelles; protein folding; protein structures; structural biology; structural elucidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Choline / metabolism*
  • Circular Dichroism
  • Humans
  • Micelles*
  • Models, Molecular
  • N-Acetylmuramoyl-L-alanine Amidase / chemistry*
  • N-Acetylmuramoyl-L-alanine Amidase / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemistry*
  • Peptides / metabolism
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / chemistry
  • Pneumococcal Infections / microbiology
  • Protein Structure, Secondary
  • Sodium Dodecyl Sulfate / chemistry
  • Streptococcus pneumoniae / chemistry*
  • Streptococcus pneumoniae / metabolism
  • Surface-Active Agents / chemistry
  • Trifluoroethanol / chemistry

Substances

  • Bacterial Proteins
  • Micelles
  • Peptides
  • Surface-Active Agents
  • Phosphorylcholine
  • Sodium Dodecyl Sulfate
  • dodecylphosphocholine
  • Trifluoroethanol
  • N-Acetylmuramoyl-L-alanine Amidase
  • Choline