Ex vivomammalian prions are formed of paired double helical prion protein fibrils

Terry, Cassandra, Wenborn, Adam, Gros, Nathalie, Sells, Jessica, Joiner, Susan, Hosszu, Laszlo L. P., Tattum, M. Howard, Panico, Silvia, Clare, Daniel K., Collinge, John, Saibil, Helen R. and Wadsworth, Jonathan D. F. (2016) Ex vivomammalian prions are formed of paired double helical prion protein fibrils. Open Biology, 6 (160035). ISSN 2046-2441

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Official URL: http://dx.doi.org/10.1098/rsob.160035

Abstract / Description

Mammalian prions are hypothesized to be fibrillar or amyloid forms of prion protein (PrP), but structures observed to date have not been definitively correlated with infectivity and the three-dimensional structure of infectious prions has remained obscure. Recently, we developed novel methods to obtain exceptionally pure preparations of prions from mouse brain and showed that pathogenic PrP in these high-titre preparations is assembled into rod-like assemblies. Here, we have used precise cell culture-based prion infectivity assays to define the physical relationship between the PrP rods and prion infectivity and have used electron tomography to define their architecture. We show that infectious PrP rods isolated from multiple prion strains have a common hierarchical assembly comprising twisted pairs of short fibres with repeating substructure. The architecture of the PrP rods provides a new structural basis for understanding prion infectivity and can explain the inability to systematically generate high-titre synthetic prions from recombinant PrP.

Item Type: Article
Uncontrolled Keywords: prion, prion disease, prion protein, prion structure, electron tomography
Subjects: 500 Natural Sciences and Mathematics > 570 Life sciences; biology
Department: School of Human Sciences
Depositing User: Cassandra Terry
Date Deposited: 19 Nov 2018 10:36
Last Modified: 19 Nov 2018 10:36
URI: http://repository.londonmet.ac.uk/id/eprint/3842

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