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

A cryo-EM structure of disease-related human Y145Stop prion protein amyloid fibrils explains species-dependent seeding barriers in prion protein amyloid propagation. 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.

Automated summary

This study presents a high-resolution cryo-EM structure of amyloid fibrils formed by human prion protein with the Y145Stop mutation associated with familial prion disease. The findings not only explain previous biochemical observations but also provide direct support for the conformational adaptability model of prion propagation.