Cryo-EM structure of disease-related prion fibrils provides insights into seeding barriers

Nat Struct Mol Biol. 2022 Oct;29(10):962-965. doi: 10.1038/s41594-022-00833-4. Epub 2022 Sep 12.

Abstract

One of the least understood aspects of prion diseases is the structure of infectious prion protein aggregates. Here we report a high-resolution cryo-EM structure of amyloid fibrils formed by human prion protein with the Y145Stop mutation that is associated with a familial prion disease. This structural insight allows us not only to explain previous biochemical findings, but also provides direct support for the conformational adaptability model of prion transmissibility barriers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid / chemistry
  • Cryoelectron Microscopy
  • Humans
  • Prion Diseases*
  • Prion Proteins / chemistry
  • Prion Proteins / genetics
  • Prion Proteins / metabolism
  • Prions* / chemistry
  • Protein Aggregates

Substances

  • Amyloid
  • Prion Proteins
  • Prions
  • Protein Aggregates