The protean prion protein

The prion protein, PrP, can adopt at least 2 conformations, the overwhelmingly prevalent cellular conformation (PrPC) and the scrapie conformation (PrPSc). PrPC features a globular C-terminal domain containing 3 α-helices and a short β-sheet and a long flexible N-terminal tail whose exact conformati...

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Bibliographic Details
Published in:PLoS biology 2020-06, Vol.18 (6), p.e3000754-e3000754
Main Author: Requena, Jesús R
Format: Article
Language:English
Subjects:
Amyloid
Analysis
Animal models
Animals
Biology and Life Sciences
Development and progression
Disease
Disease Models, Animal
Helices
Humans
Hydrogen bonds
Medicine and Health Sciences
Mice
Mice, Transgenic
Mutation
Neurodegeneration
Polypeptides
Primer
Prion Diseases
Prion protein
Prion Proteins
Prions
Protein structure
Proteins
Research and Analysis Methods
Scrapie
Severe acute respiratory syndrome coronavirus 2
Structure
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Summary:The prion protein, PrP, can adopt at least 2 conformations, the overwhelmingly prevalent cellular conformation (PrPC) and the scrapie conformation (PrPSc). PrPC features a globular C-terminal domain containing 3 α-helices and a short β-sheet and a long flexible N-terminal tail whose exact conformation in vivo is not yet known and a metastable subdomain with β-strand propensity has been identified within it. The PrPSc conformation is very rare and has the characteristics of an amyloid. Furthermore, PrPSc is a prion, i.e., it is infectious. This involves 2 steps: (1) PrPSc can template PrPC and coerce it to adopt the PrPSc conformation and (2) PrPSc can be transmitted between individuals, by oral, parenteral, and other routes and thus propagate as an infectious agent. However, this is a simplification: On the one hand, PrPSc is not a single conformation, but rather, a set of alternative similar but distinct conformations. Furthermore, other amyloid conformations of PrP exist with different biochemical and propagative properties. In this issue of PLOS Biology, Asante and colleagues describe the first murine model of familial human prion disease and demonstrate the emergence and propagation of 2 PrP amyloid conformers. Of these, one causes neurodegeneration, whereas the other does not. With its many conformers, PrP is a truly protean protein.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3000754