The Structure of Mammalian Prions and Their Aggregates.

Prion diseases, such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), and sheep scrapie, are caused by the misfolding of the cellular prion protein (PrP ^C ) into a disease-causing conformer (PrP ^Sc ). PrP ^C is a normal, GPI-anchored protein that is expressed on the surface of neurons and other cell types. The structure of PrP ^C is well understood, based on studies of recombinant PrP, which closely mimics the structure of native PrP ^C . In contrast, PrP ^Sc is prone to aggregate into a variety of quaternary structures, such as oligomers, amorphous aggregates, and amyloid fibrils. The propensity of PrP ^Sc to assemble into these diverse forms of aggregates is also responsible for our limited knowledge about its structure. Then again, the repeating nature of certain regular PrP ^Sc aggregates has allowed (lower resolution) insights into the structure of the infectious conformer, establishing a four-rung β-solenoid structure as a key element of its architecture.
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