N-terminal domain of prion protein directs its oligomeric association

Trevitt, Clare R. and Hosszu, Laszlo L.P. and Batchelor, Mark and Panico, Silvia and Terry, Cassandra and Nicoll, Andrew J. and Risse, Emmanuel and Taylor, William A. and Sandberg, Malin K. and Al-Doujaily, Huda and Linehan, Jacqueline M. and Saibil, Helen R. and Scott, David J. and Collinge, John and Waltho, Jonathan P. and Clarke, Anthony R. (2014) N-terminal domain of prion protein directs its oligomeric association. Journal of Biological Chemistry, 289 (37). pp. 25497-25508. ISSN 1083-351X

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Abstract

The self-association of prion protein (PrP) is a critical step in the pathology of prion diseases. It is increasingly recognized that small non-fibrillar β-sheet-rich oligomers of PrP may be of crucial importance in the prion disease process. Here, we characterize the structure of a well defined β-sheet-rich oligomer, containing ∼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
Additional Information: This research was originally published in Journal of Biological Chemistry. Clare R. Trevitt, Laszlo L. P. Hosszu, Mark Batchelor, Silvia Panico, Cassandra Terry, Andrew J. Nicoll, Emmanuel Risse, William A. Taylor, Malin K. Sandberg, Huda Al-Doujaily, Jacqueline M. Linehan, Helen R. Saibil, David J. Scott, John Collinge, Jonathan P. Waltho and Anthony R. Clarke. N-terminal domain of prion protein directs its oligomeric association. Journal of Biological Chemistry. 2014; Vol. 289, no. 37, pp. 25497-25508. © the American Society for Biochemistry and Molecular Biology.
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Biosciences
Identification Number: 10.1074/jbc.M114.566588
Depositing User: Scott, David
Date Deposited: 21 Apr 2017 12:42
Last Modified: 23 Apr 2017 04:16
URI: http://eprints.nottingham.ac.uk/id/eprint/41968

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