Amyloid aggregates of the prion peptide PrP106-126 are destabilised by oxidation and by the action of dendrimers.
The prion protein (PrP) peptide 106-126 forms amyloid aggregates in vitro and this sequence is speculated to be involved in the formation of amyloid fibrils by the abnormally folded PrP protein (PrPSc) found in spongiform encephalopathies. It is shown here by incubation experiments in water using Thioflavin T (ThT) as a fluorescent probe for amyloid formation that changes in C-terminal charge, oxidation state and conformational stabilisation lead to large changes in amyloid forming behaviour (amyloidogenicity) of this peptide. Amyloid formation is favoured by a charged C-terminus and is strongly inhibited by oxidation. Furthermore, cationic dendrimers are shown to perturb peptide fibrillation in a process dependent on the nature of the charged groups on the dendrimer surface.
Heegaard
Peter M H
PM
Department of Veterinary Diagnostics and Research, Danish Institute for Food and Veterinary Research, 27, Bülowsvej, DK 1790 Copenhagen V, Denmark. pmhh@dfvf.dk
Pedersen
Heidi Gertz
HG
Flink
James
J
Boas
Ulrik
U
D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins
D000682:Amyloid; D011328:Prions; D011994:Recombinant Proteins; C466227:miniprion protein PrP106, mouse