Cryo-EM structure of an amyloid fibril formed by full-length human prion protein

Nat Struct Mol Biol. 2020 Jun;27(6):598-602. doi: 10.1038/s41594-020-0441-5. Epub 2020 Jun 8.


Prion diseases are caused by the misfolding of prion protein (PrP). Misfolded PrP forms protease-resistant aggregates in vivo (PrPSc) that are able to template the conversion of the native form of the protein (PrPC), a property shared by in vitro-produced PrP fibrils. Here we produced amyloid fibrils in vitro from recombinant, full-length human PrPC (residues 23-231) and determined their structure using cryo-EM, building a model for the fibril core comprising residues 170-229. The PrP fibril consists of two protofibrils intertwined in a left-handed helix. Lys194 and Glu196 from opposing subunits form salt bridges, creating a hydrophilic cavity at the interface of the two protofibrils. By comparison with the structure of PrPC, we propose that two α-helices in the C-terminal domain of PrPC are converted into β-strands stabilized by a disulfide bond in the PrP fibril. Our data suggest that different PrP mutations may play distinct roles in modulating the conformational conversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Cryoelectron Microscopy
  • Disulfides / chemistry
  • Humans
  • Models, Molecular
  • PrPC Proteins / chemistry*
  • PrPC Proteins / genetics
  • PrPC Proteins / metabolism*
  • Protein Conformation


  • Amyloid
  • Disulfides
  • PrPC Proteins