All or none fibrillogenesis of a prion peptide.
Amyloid proteins and peptides comprise a diverse group of molecules that vary both in size and amino-acid sequence, yet assemble into amyloid fibrils that have a common core structure. Kinetic studies of amyloid fibrillogenesis have revealed that certain amyloid proteins form oligomeric intermediates prior to fibril formation. We have investigated fibril formation with a peptide corresponding to residues 195-213 of the human prion protein. Through a combination of kinetic and equilibrium studies, we have found that the fibrillogenesis of this peptide proceeds as an all-or-none reaction where oligomeric intermediates are not stably populated. This variation in whether oligomeric intermediates are stably populated during fibril formation indicates that amyloid proteins assemble into a common fibrillar structure; however, they do so through different pathways.
Zou
W Q
WQ
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada.
Yang
D S
DS
Fraser
P E
PE
Cashman
N R
NR
Chakrabartty
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D004735:Energy Transfer; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009282:Naphthalenesulfonates; D009391:Nephelometry and Turbidimetry; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence
D009282:Naphthalenesulfonates; D010446:Peptide Fragments; D011328:Prions; C048876:1,5-AEDANS