Biochemical and structural studies of the prion protein polymorphism

FEBS Letters

Olmedo, Maria I.¹  Petchanikow, Cyril²  Anderes, Laurence²  Frossard, Marie-Jose²  Soto, Claudio²  Saborio, Gabriela P.² 

[1] Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Millenium Institute for Advanced Studies in Cell Biology and Biotechnology, Santiago, Chile;Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva, Switzerland

关键词: Prion;    Transmissible spongiform encephalopathy;    Protein structure;    Creutzfeldt–Jakob disease;    Circular dichroism;    TSE;    transmissible spongiform encephalopathies;    CJD;    Creutzfeldt–Jakob disease;    GSS;    Gerstmann–Straussler syndrome;    FFI;    fatal familial insomnia;    PrPC;    cellular prion protein;    PrPSc;    scrapie prion protein;    CD;    circular dichroism;    TFE;    trifluoroethanol;    ThT;    thioflavine T;   

DOI  :  10.1016/S0014-5793(01)03147-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 β-sheet-rich structure similar to the pathological protein. Circular dichroism studies showed that the methionine-containing peptide has a greater propensity to adopt a β-sheet conformation in a variety of experimental conditions. The higher β-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.

【 授权许可】

Unknown