De novo design of a two-stranded coiled-coil switch peptide

J Struct Biol. 2006 Aug;155(2):146-53. doi: 10.1016/j.jsb.2006.01.017. Epub 2006 May 20.

Abstract

The properties and characteristics shared by amyloid fibrils formed from disease and non-disease associated proteins that are unrelated in sequence and structure offer the prospect that model systems can be used to systematically assess the factors that predispose a native protein to form amyloid fibrils. Based on a de novo design approach, we recently reported a unique switch peptide model system, ccbeta, that forms a three-stranded coiled-coil structure at low temperatures and which can be easily converted to amyloid fibrils by increasing the temperature. To simplify the system further, we describe here the redesign of a two-stranded ccbeta coiled-coil variant and its detailed analysis by a variety of biophysical methods. Compared with the original design, the characteristics of the peptide make it even simpler to elucidate and validate fundamental principles of amyloid fibril-formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Amyloid / chemistry
  • Animals
  • Circular Dichroism
  • Humans
  • Macromolecular Substances / chemistry
  • Mice
  • Microscopy, Electron, Transmission / methods
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein Structure, Secondary*
  • Sequence Homology, Amino Acid
  • Temperature

Substances

  • Amino Acids
  • Amyloid
  • Macromolecular Substances
  • Peptides