Ex vivo mammalian prions are formed of paired double helical prion protein fibrils
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2016-05-04
Date Acceptance
2016-04-13
Citation
Open Biology, 2016, 6 (5)
ISSN
2046-2441
Publisher
The Royal Society
Journal / Book Title
Open Biology
Volume
6
Issue
5
Copyright Statement
© 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.
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
prion
prion disease
prion protein
prion structure
electron tomography
SCRAPIE PRIONS
DISEASE
STRAINS
TRANSMISSION
PROPAGATION
MODEL
TITER
ASSAY
Publication Status
Published
Article Number
160035