Related Experiment Video

Updated: Jul 7, 2026

Protein Misfolding Cyclic Amplification of Prions
10:12

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

Protein-only transmission of three yeast prion strains

Chih-Yen King1, Ruben Diaz-Avalos

  • 1Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306, USA. chihyen@sb.fsu.edu

Nature
|March 19, 2004
PubMed

Insights

This study demonstrates that prion strains are protein-only, using a yeast model. Different folding patterns of the same protein encode distinct prion strain information, propagating infectivity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Prions are infectious proteins implicated in neurodegenerative diseases.
  • Key questions remain about how distinct prion strains arise from a single protein and their fundamental composition.
  • The yeast [PSI] genetic element, a model prion, enhances nonsense mutation read-through.

Purpose of the Study:

  • To investigate the protein-only nature of prion strains.
  • To determine if different prion strains are encoded by distinct folding patterns of the same protein.
  • To demonstrate de novo generation of prion infectivity in vitro.

Main Methods:

  • Purification of infectious fibrous aggregates of the Sup35 prion protein from yeast.
  • In vitro generation of elongated amyloid fibers using purified aggregates as seeds.
  • Electron microscopy and electron diffraction to analyze fiber structure.
  • Introduction of in vitro generated fibers into yeast hosts to assess infectivity.

Main Results:

  • Infectious amyloid fibers were generated in vitro from purified yeast prion seeds.
  • In vitro generated fibers exhibited strain-specific infectivity when introduced into yeast.
  • Electron microscopy and diffraction confirmed the cross-beta amyloid structure of the fibers, consistent with the seeds.
  • The morphology of in vitro generated fibers was indistinguishable from the original yeast seeds.

Conclusions:

  • Prion strains are indeed protein-only entities.
  • Distinct prion strain information is encoded within different, self-propagating cross-beta folding patterns of the Sup35 protein.
  • This study provides strong evidence for the structural basis of prion strain diversity and propagation.

More Related Videos

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans12:57

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

Published on: January 8, 2015

High-throughput Screening for Protein-based Inheritance in S. cerevisiae08:12

High-throughput Screening for Protein-based Inheritance in S. cerevisiae

Published on: August 8, 2017

Related Concept Videos

Yeast Signaling01:28

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Fungal Phylum Microsporidia01:28

Fungal Phylum Microsporidia

Microsporidia are a group of obligate intracellular fungi that were initially classified as protists but were later reclassified based on phylogenetic, molecular, and structural evidence linking them to the Chytridiomycota. These unicellular, non-motile organisms are highly specialized parasites that infect a wide range of animal hosts, including humans. They have evolved extensive genomic and metabolic reductions, making them highly dependent on their hosts for survival.Morphology and Genomic...
Subviral Agents01:29

Subviral Agents

Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
Transmission of Pathogens01:24

Transmission of Pathogens

Pathogens spread from their reservoirs to susceptible hosts through three main routes: contact transmission, vehicle transmission, and vector transmission. Each route involves distinct mechanisms of transfer.Contact TransmissionThis category includes direct contact, indirect contact, and droplet transmission:Direct contact involves immediate physical interaction between individuals—such as a handshake—which can spread pathogens like Streptococcus pyogenes, the bacterium responsible for...
Plague01:24

Plague

Plague is a highly virulent zoonotic disease caused by Yersinia pestis, a Gram-negative, facultatively anaerobic coccobacillus. This pathogen primarily circulates among rodent populations and is transmitted to humans through the bite of infected fleas. Additional transmission routes include direct contact with infected animal tissue or inhalation of respiratory droplets from individuals with pneumonic plague. These multiple transmission pathways highlight the bacterium’s potential for rapid...