Familial Prion Disease Mutation Alters the Secondary Structure of Recombinant Mouse Prion Protein: Implications for the Mechanism of Prion Formation

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• 作者：Roberto Cappai ; Leanne Stewart ; Michael F. Jobling ; James M. Thyer ; Anthony R. White ; Konrad Beyreuther ; Steven J. Collins ; Colin L. Masters ; and Colin J. Barrow
• 刊名：Biochemistry
• 出版年：1999
• 出版时间：March 16, 1999
• 年：1999
• 卷：38
• 期：11
• 页码：3280 - 3284
• 全文大小：59K
• 年卷期：v.38,no.11(March 16, 1999)
• ISSN：1520-4995

文摘

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 nucleicacid. Prions are believed to propagate by changing the conformation of the normal cellular prion protein(PrP^c) into an infectious isoform without altering the primary sequence. Proteins equivalent to the matureform of the wild-type mouse prion protein (residues 23-231) or with a mutation equivalent to that associatedwith 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 ofthe mouse prion proteins. The wild-type and mutant proteins were analyzed by circular dichroism underdifferent pH and temperature conditions. The mutation was associated with a decrease in -helical content,while the -sheet content of the two proteins was unchanged. This suggests the mutation, while alteringthe secondary structure of PrP, is not sufficient to induce proteinase K resistance and could thereforerepresent an intermediate isoform along the pathway toward prion formation.