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Familial prion disease mutation alters the secondary structure of recombinant mouse prion protein: implications for the mechanism of prion formation

journal contribution
posted on 1999-03-01, 00:00 authored by R Cappai, L Stewart, M F Jobling, J M Thyer, A R White, K Beyreuther, S J Collins, C L Masters, Colin BarrowColin Barrow
A considerable body of data supports the model that the infectious agent (called a prion) which causes the transmissible spongiform encephalopathies is a replicating polypeptide devoid of nucleic acid. Prions are believed to propagate by changing the conformation of the normal cellular prion protein (PrPc) into an infectious isoform without altering the primary sequence. Proteins equivalent to the mature form of the wild-type mouse prion protein (residues 23-231) or with a mutation equivalent to that associated with Gerstmann-Straüssler-Scheinker disease (proline to leucine at codon 102 in human; 101 in mouse) were expressed in E. coli. The mutation did not alter the relative proteinase K susceptibility properties of the mouse prion proteins. The wild-type and mutant proteins were analyzed by circular dichroism under different pH and temperature conditions. The mutation was associated with a decrease in alpha-helical content, while the beta-sheet content of the two proteins was unchanged. This suggests the mutation, while altering the secondary structure of PrP, is not sufficient to induce proteinase K resistance and could therefore represent an intermediate isoform along the pathway toward prion formation.

History

Journal

Biochemistry

Volume

38

Issue

11

Pagination

3280 - 3284

Publisher

American Chemical Society

Location

Washington, D.C.

ISSN

0006-2960

eISSN

1520-4995

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1999, American Chemical Society