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N-terminal Domain of Prion Protein Directs Its Oligomeric Association

Trevitt, Clare R.; Hosszu, Laszlo L.P.; Batchelor, Mark; Panico, Silvia; Terry, Cassandra; Nicoll, Andrew J.; Risse, Emmanuel; Taylor, William A.; Sandberg, Malin K.; Al-Doujaily, Huda; Linehan, Jacqueline M.; Saibil, Helen R.; Scott, David J.; Collinge, John; Waltho, Jonathan P.; Clarke, Anthony R.


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

Associate Professor & Reader Inphysical Biochemistry

John Collinge

Jonathan P. Waltho

Anthony R. Clarke


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.


Trevitt, C. R., Hosszu, L. L., Batchelor, M., Panico, S., Terry, C., Nicoll, A. J., …Clarke, A. R. (2014). N-terminal Domain of Prion Protein Directs Its Oligomeric Association. Journal of Biological Chemistry, 289(37), 25497-25508.

Journal Article Type Article
Acceptance Date Jul 14, 2014
Online Publication Date Jul 29, 2014
Publication Date Sep 12, 2014
Deposit Date Apr 21, 2017
Publicly Available Date Apr 21, 2017
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 289
Issue 37
Pages 25497-25508
Public URL
Publisher URL
Copyright Statement Copyright information regarding this work can be found at the following address:
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.


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Copyright Statement
Copyright information regarding this work can be found at the following address:

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