The Structure of PrP Prions.

PrP (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. PrP is an alternatively folded variant of the cellular prion protein, PrP, which is a regular, GPI-anchored protein that is present on the cell surface of neurons and other cell types. While the structure of PrP is well studied, the structure of PrP 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 PrP as a four-rung β-solenoid. A high-resolution structure of PrP 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 PrP. Here, we summarize the current knowledge regarding the structure of PrP and speculate about the molecular conversion mechanisms that leads from PrP to PrP.