Effect of copper on recombinant mouse prion protein

Wong, Boon Seng; Brown, David R.; Clive, Christine; Haswell, Steve J.; Sy, Man‐Sun; Williamson, R. Anthony; Burton, Dennis R.; Jones, Ian M.

doi:10.1042/bst028a036b

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structural studies have shown evidence for hydrogen bonding between Asp178 and Tyr128, which might provide a structural basis for the influence of the polymorphism on the disease phenotype that segregates with the mutation Asp178Asn [45]. In addition, it has been reported that a slightly different conformation of recombinant Met‐ or Val‐containing PrP isoforms was induced upon copper binding [46].…”

Section: Discussionmentioning

confidence: 99%

Biochemical and structural studies of the prion protein polymorphism

Petchanikow¹,

Saborı́o²,

Anderes³

et al. 2001

FEBS Letters

View full text Add to dashboard Cite

A hallmark event in transmissible spongiform encephalopathies is the conversion of the physiological prion protein into the disease-associated isoform. A natural polymorphism at codon 129 of the human prion gene, resulting in either methionine or valine, has profound influence on susceptibility and phenotypic expression of the disease in humans. In this study, we investigated the local propensity of synthetic peptides, corresponding to the region of the polymorphism and containing either methionine or valine, to adopt a L L-sheet-rich structure similar to the pathological protein. Circular dichroism studies showed that the methionine-containing peptide has a greater propensity to adopt a L L-sheet conformation in a variety of experimental conditions. The higher L L-sheet tendency of this peptide was also associated with an increased ability to aggregate into amyloid-like fibrils. These results suggest that methionine at position 129 of the prion protein increases its susceptibility to switch to the abnormal conformation, in comparison with the presence of valine at the same position. ß

show abstract

Section: Discussionmentioning

confidence: 99%