title: The Structure of Mammalian Prions and Their Aggregates.
abstract: 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 (PrPC) into a disease-causing conformer (PrPSc). PrPCis a normal, GPI-anchored protein that is expressed on the surface of neurons and other cell types. The structure of PrPCis well understood, based on studies of recombinant PrP, which closely mimics the structure of native PrPC. In contrast, PrPScis prone to aggregate into a variety of quaternary structures, such as oligomers, amorphous aggregates, and amyloid fibrils. The propensity of PrPScto 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 PrPScaggregates 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.
authors.affiliation: University of Alberta, Edmonton, AB, Canada; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Vázquez-Fernández
authors.affiliation: University of Alberta, Edmonton, AB, Canada.
authors.forename: H S
authors.initials: HS
authors.lastname: Young
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, Santiago de Compostela, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Requena
authors.affiliation: University of Alberta, Edmonton, AB, Canada; Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada. Electronic address: wille@ualberta.ca.
authors.forename: H
authors.initials: H
authors.lastname: Wille
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000818:Animals; D003460:Crystallization; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D066329:Protein Aggregates
chemical_list: D000682:Amyloid; D011328:Prions; D066329:Protein Aggregates
keywords: Amyloid fibril; Cross-β structure; Neurodegeneration; Protein misfolding; Templating; β-Solenoid structure