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Ex vivo mammalian prions are formed of paired double helical prion protein fibrils

Terry, C; Wenborn, A; Gros, N; Sells, J; Joiner, S; Hosszu, LL; Tattum, MH; ... Wadsworth, JD; + view all (2016) Ex vivo mammalian prions are formed of paired double helical prion protein fibrils. Open Biology , 6 (5) 10.1098/rsob.160035. Green open access

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Abstract

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.

Type: Article
Title: Ex vivo mammalian prions are formed of paired double helical prion protein fibrils
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1098/rsob.160035
Publisher version: http://dx.doi.org/10.1098/rsob.160035
Additional information: © 2016 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Keywords: electron tomography, prion, prion disease, prion protein, prion structure
URI: http://discovery.ucl.ac.uk/id/eprint/1499757
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