Recent advances in understanding mammalian prion structure

Terry, Cassandra and Wadsworth, Jonathan D. F. (2019) Recent advances in understanding mammalian prion structure. Frontiers in molecular neuroscience, 12 (169). pp. 1-7. ISSN 1662-5099

[img]
Preview
Text (Invited article to publish)
fnmol-12-00169.pdf - Published Version
Available under License Creative Commons Attribution 4.0.

Download (1MB) | Preview
Official URL: https://www.frontiersin.org/articles/10.3389/fnmol...

Abstract / Description

Prions are lethal pathogens, which cause fatal neurodegenerative diseases in mammals. They are unique infectious agents and are composed of self-propagating multi-chain assemblies of misfolded host-encoded prion protein (PrP). Understanding prion structure is fundamental to understanding prion disease pathogenesis however to date, the high-resolution structure of authentic ex vivo infectious prions remains unknown. Advances in determining prion structure have been severely impeded by the difficulty in recovering relatively homogeneous prion particles from infected brain and definitively associating infectivity with the PrP assembly state. Recently, however, images of highly infectious ex vivo PrP rods that produce prion-strain specific disease phenotypes in mice have been obtained using cryo-electron microscopy and atomic force microscopy. These images have provided the most detailed description of ex vivo mammalian prions reported to date and have established that prions isolated from multiple strains have a common hierarchical structure. Misfolded PrP is assembled into 20 nm wide rods containing two fibers, each with double helical repeating substructure, separated by a characteristic central gap 8-10 nm in width. Irregularly structured material with adhesive properties distinct to that of the fibers is present within the central gap of the rod. Prions are clearly distinguishable from non-infectious recombinant PrP fibrils generated in vitro and from all other propagating protein structures so far described in other neurodegenerative diseases. The basic architecture of mammalian prions appears to be exceptional and fundamental to their lethal pathogenicity.

Item Type: Article
Uncontrolled Keywords: Alzheimer’s disease; prion disease; prion, prion-like; prion structure; amyloid beta; α-synuclein; tau
Subjects: 500 Natural Sciences and Mathematics > 570 Life sciences; biology
Department: School of Human Sciences
Depositing User: Cassandra Terry
Date Deposited: 10 Sep 2020 08:44
Last Modified: 10 Sep 2020 08:44
URI: http://repository.londonmet.ac.uk/id/eprint/6036

Downloads

Downloads per month over past year



Downloads each year

Actions (login required)

View Item View Item