De novo design of a two-stranded coiled-coil switch peptide.
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.
Kammerer
Richard A
RA
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 PT, UK. richard.kammerer@manchester.ac.uk
Steinmetz
Michel O
MO
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000682:Amyloid / Q000737:chemistry; D000818:Animals; D002942:Circular Dichroism; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013696:Temperature
D000596:Amino Acids; D000682:Amyloid; D046911:Macromolecular Substances; D010455:Peptides