Shift of fibril-forming ability of the designed alpha-helical coiled-coil peptides into the physiological pH region

Protein Eng. 2003 Dec;16(12):1125-30. doi: 10.1093/protein/gzg138.


Recently, we designed a short alpha-helical fibril-forming peptide (alphaFFP) that can form alpha-helical nanofibrils at acid pH. The non-physiological conditions of the fibril formation hamper biomedical application of alphaFFP. It was hypothesized that electrostatic repulsion between glutamic acid residues present at positions (g) of the alphaFFP coiled-coil sequence prevent the fibrillogenesis at neutral pH, while their protonation below pH 5.5 triggers axial growth of the fibril. To test this hypothesis, we synthesized alphaFFPs where all glutamic acid residues were substituted by glutamines or serines. The electron microscopy study confirmed that the modified alphaFFPs form nanofibrils in a wider range of pH (2.5-11). Circular dichroism spectroscopy, sedimentation, diffusion and differential scanning calorimetry showed that the fibrils are alpha-helical and have elongated and highly stable cooperative tertiary structures. This work leads to a better understanding of interactions that control the fibrillogenesis of the alphaFFPs and opens opportunities for their biomedical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry
  • Circular Dichroism
  • Hydrogen-Ion Concentration
  • Microscopy, Electron
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Peptide Fragments / ultrastructure
  • Protein Structure, Secondary


  • Peptide Fragments