Related Experiment Video

Updated: Jun 14, 2026

Protein Misfolding Cyclic Amplification of Prions
10:12

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

Mammalian prions generated from bacterially expressed prion protein in the absence of any mammalian cofactors

Jae-Il Kim1, Ignazio Cali, Krystyna Surewicz

  • 1Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA.

The Journal of Biological Chemistry
|March 23, 2010
PubMed

Insights

Researchers generated infectious prions solely from recombinant prion protein, providing strong evidence for the protein-only hypothesis of transmissible spongiform encephalopathies (TSEs). This study demonstrates that cofactors are not essential for prion propagation.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases linked to prion protein misfolding.
  • The protein-only hypothesis posits that misfolded prion protein (PrPSc) is the infectious agent.
  • Previous prion propagation methods required cofactors like nucleic acids or lipids.

Purpose of the Study:

  • To investigate if infectious prions can be generated without non-protein cofactors.
  • To provide definitive support for the protein-only hypothesis of TSEs.

Main Methods:

  • Utilized a modified protein misfolding cyclic amplification (PMCA) technique.
  • Employed highly purified, bacterially expressed recombinant hamster prion protein.
  • Conducted experiments without mammalian or synthetic cofactors, using only buffer salts and detergent.

Main Results:

  • Successfully generated infectious prions from recombinant prion protein alone.
  • Demonstrated prion propagation in wild-type hamsters using these de novo generated prions.
  • Showed that nucleic acids, polyanions, or lipids are not obligatory for prion conversion.

Conclusions:

  • The findings strongly support the protein-only hypothesis for TSE pathogenesis.
  • This research indicates that cofactors are non-essential for the conversion of prion protein into its infectious form.
  • Presents a simplified model for prion replication and disease mechanism studies.

More Related Videos

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

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

Related Concept Videos

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...
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...
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...