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Pathogens. 2018 Feb 7;7(1). pii: E20. doi: 10.3390/pathogens7010020.

The Structure of PrPSc Prions.

Author information

1
Centre for Prions and Protein Folding Diseases & Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2M8, Canada. wille@ualberta.ca.
2
CIMUS Biomedical Research Institute & Department of Medical Sciences, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain. jesus.requena@usc.es.

Abstract

PrPSc (scrapie isoform of the prion protein) prions are the infectious agent behind diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (deer, elk, moose, and reindeer), as well as goat and sheep scrapie. PrPSc is an alternatively folded variant of the cellular prion protein, PrPC, which is a regular, GPI-anchored protein that is present on the cell surface of neurons and other cell types. While the structure of PrPC is well studied, the structure of PrPSc resisted high-resolution determination due to its general insolubility and propensity to aggregate. Cryo-electron microscopy, X-ray fiber diffraction, and a variety of other approaches defined the structure of PrPSc as a four-rung β-solenoid. A high-resolution structure of PrPSc still remains to be solved, but the four-rung β-solenoid architecture provides a molecular framework for the autocatalytic propagation mechanism that gives rise to the alternative conformation of PrPSc. Here, we summarize the current knowledge regarding the structure of PrPSc and speculate about the molecular conversion mechanisms that leads from PrPC to PrPSc.

KEYWORDS:

PrPSc; amyloid; cryo-electron microscopy; prion propagation; prion structure; β-solenoid

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