Copper(II)-induced conformational changes and protease resistance in recombinant and cellular PrP - Effect of protein age and deamidation
2000 | journal article. A publication with affiliation to the University of Göttingen.
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Copper(II)-induced conformational changes and protease resistance in recombinant and cellular PrP - Effect of protein age and deamidation
Qin, K. F.; Yang, D. S.; Yang, Y.; Chishti, M. A.; Meng, L. J.; Kretzschmar, H. A. & Yip, C. M. et al. (2000)
Journal of Biological Chemistry, 275(25) pp. 19121-19131. DOI: https://doi.org/10.1074/jbc.275.25.19121
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- Authors
- Qin, K. F.; Yang, D. S.; Yang, Y.; Chishti, M. A.; Meng, L. J.; Kretzschmar, Hans A.; Yip, C. M.; Fraser, Paul E.; Westaway, D.
- Abstract
- While PrPC rearranges in the area of codons 104-113 to form PrPSc during prion infections, the events that initiate sporadic Creutzfeldt-Jakob disease are undefined. AS Cu(II) is a putative ligand for PrPC and has been implicated in the pathogenesis of Creutzfeldt-Jakob disease and other neurodegenerative diseases, we investigated the structural effects of binding. Incubation of brain microsomes with Cu(II) generated similar to 30-kDa proteinase K-resistant PrP. Cu(II) had little effect on fresh recombinant PrP23-231, but aged protein characterized by conversion of Asn-107 to Asp decreased cu-helical content by similar to 30%, increased beta-sheet content 100%, formed aggregates, and acquired proteinase K resistance in the presence of Cu(II), These transitions took place without need for acid pH, organic solvents, denaturants, or reducing agents. Since conversion of Asn to Asp proceeds by a spontaneous pathway involving deamidation, our data suggest that covalent variants of PrPC arising in this manner may, in concert with Cu(II), generate PrPSc-like species capable of initiating sporadic prion disease.
- Issue Date
- 2000
- Status
- published
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Journal
- Journal of Biological Chemistry
- ISSN
- 0021-9258