Structural autonomy of a β-hairpin peptide derived from the pneumococcal choline-binding protein LytA

Protein Eng Des Sel. 2011 Jan;24(1-2):113-22. doi: 10.1093/protein/gzq087. Epub 2010 Nov 4.

Abstract

The cell wall of Streptococcus pneumoniae and several other micro-organisms is decorated with a number of the so-called choline-binding proteins (CBPs) that recognise the choline residues in the bacterial surface by means of highly conserved, concatenated 20-aa sequences termed choline-binding repeats (CBRs), that are composed of a loop and a β-hairpin structure. In this work, we have investigated the ability to fold in aqueous solution of a 14-aa peptide (LytA₁₉₇₋₂₁₀[wt]) and a single derivative of it, LytA₁₉₇₋₂₁₀[ND], corresponding to one of the six β-hairpins of the LytA pneumococcal amidase. Intrinsic fluorescence and circular dichroism spectroscopical measurements showed that both peptides spontaneously acquire a non-random conformation which is also able to bind the natural ligand choline. Furthermore, nuclear magnetic resonance techniques allowed the calculation of the structure of the LytA₁₉₇₋₂₁₀[ND] peptide, which displayed a β-hairpin conformation highly similar to that found within the full-length C-LytA module. These results provide a structural basis for the modular organisation of CBPs and suggest the use of CBRs as new templates for the design of stable β-hairpins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / chemistry*
  • Amidohydrolases / metabolism
  • Amino Acid Sequence
  • Choline / metabolism
  • Enzyme Stability
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Structure, Secondary
  • Streptococcus pneumoniae / chemistry
  • Streptococcus pneumoniae / enzymology*

Substances

  • Peptides
  • Amidohydrolases
  • amidase
  • Choline