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    N-terminal domain of Prion Protein directs its Oligomeric Association

    Trevitt, C.R. and Hosszu, L.L.P. and Batchelor, M. and Panico, S. and Terry, C. and Nicoll, A.J. and Risse, E. and Taylor, W.A. and Sandberg, M.K. and Al-Doujaily, H. and Linehan, J.M. and Saibil, Helen R. and Scott, D.J. and Collinge, J. and Waltho, J.P. and Clarke, A.R. (2014) N-terminal domain of Prion Protein directs its Oligomeric Association. Journal of Biological Chemistry 289 , pp. 25497-25508. ISSN 0021-9258.

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    The self-association of prion protein (PrP) is a critical step in the pathology of prion diseases. It is increasingly recognised that small non-fibrillar β-sheet-rich oligomers of PrP may be of crucial importance in the prion disease process. Here, we characterise the structure of a well-defined β-sheet-rich oligomer, containing approximately 12 PrP molecules, and often enclosing a central cavity, formed using full-length recombinant PrP. The N-terminal region of prion protein (residues 23-90) is required for the formation of this distinct oligomer; a truncated form comprising residues 91-231 forms a broad distribution of aggregated species. No infectivity or toxicity was found using cell and animal model systems. This study demonstrates that examination of the full repertoire of conformers and assembly states that can be accessed by PrP under specific experimental conditions should ideally be done using the full-length protein.


    Item Type: Article
    Keyword(s) / Subject(s): CJD, Prions, β-PrP, Molten Globule, β-sheet, Amyloid, Oligomer, Protein Folding, Protein Aggregation, Intrinsically Disordered Proteins
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 31 Jul 2014 08:05
    Last Modified: 02 Aug 2023 17:12


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