Prion protein conversion in vitro

@article{Supattapone2004PrionPC,
  title={Prion protein conversion in vitro},
  author={Surachai Supattapone},
  journal={Journal of Molecular Medicine},
  year={2004},
  volume={82},
  pages={348-356}
}
  • S. Supattapone
  • Published 10 March 2004
  • Biology
  • Journal of Molecular Medicine
The infectious agents of prion diseases are composed primarily of an infectious protein designated PrPSc. In cells infected with prions, a host glycoprotein termed PrPC undergoes induced conformational change to PrPSc, but the molecular mechanism underlying this structural transition occurs remains unknown. The prion-seeded conversion of PrPC to protease-resistant PrPSc-like molecules (PrPres) has been studied both in crude and purified in vitro systems in order to investigate the mechanism of… 

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
Results indicate that there is selectivity in the species generated by interaction with different molecules of RNA, and the catalytic effect of RNA on the PrPC→PrPSc conversion depends on the RNA sequence, and small RNA molecules may exert a protective effect.

Prions: protein only or something more? Overview of potential prion cofactors.

TLDR
Recent findings such as the cellular factors that might be involved in the conformational conversion of prion proteins and the potential mechanisms by which they could operate are discussed.

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TLDR
Current knowledge about the biochemical nature of the prion infectious agent and structure of PrPSc is summarized, potential strategies for generating prion infectivity de’novo are described and some insight is provided on why the reconstitution of infectivity has been difficult to achieve in’vitro.

Aspects of prion protein dynamics in cell culture models

TLDR
The results indicate that perturbation of PrPsc glycoform profile in an infectious source does not lead to a correlated perturbations of glyco Form profile in the newly established infection, and therefore the glycosylation ofPrPsc in a infectious source is not a required source of information for establishing the glyco form profile of a Prion infection.
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References

SHOWING 1-10 OF 76 REFERENCES

RNA molecules stimulate prion protein conversion

TLDR
It is reported that stoichiometric transformation of PrPC to PrPres in vitro requires specific RNA molecules, suggesting that host-encoded stimulatory RNA molecules may have a role in the pathogenesis of prion disease.

Cell-free formation of protease-resistant prion protein

TLDR
The conversion of PrPc to protease-resistant forms similar to PrPSc in a cell-free system composed of substantially purified constituents is reported, providing direct evidence that PrP sc derives from specific PrP c–PrPSc interactions.

Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding

TLDR
The method could be applied to diagnose the presence of currently undetectable prion infectious agent in tissues and biological fluids, and may provide a unique opportunity to determine whether PrPSc replication results in the generation of infectivity in vitro.

In vitro amplification of protease-resistant prion protein requires free sulfhydryl groups.

TLDR
Using an in vitro PrP(Sc) amplification technique adapted from protein misfolding cyclic amplification (PMCA), the first evidence that a reactive chemical group plays an essential role in the conformational change from Pr(C) to PrP (Sc) is provided.

Reconstitution of Prion Infectivity from Solubilized Protease-resistant PrP and Nonprotein Components of Prion Rods*

TLDR
Preliminary results suggest that infectivity can be greatly increased by combining nonaggregated protease-resistant PrP with heparan sulfate, a known component of amyloid plaques in the brain.

Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms.

TLDR
The modulating effect of the polymorphisms in PrPC and PrPSc on the cell-free conversion characteristics suggests that, besides the species barrier, polymorphism barriers play a significant role in the transmissibility of prion diseases.

Prion‐Protein‐Specific Aptamer Reduces PrPSc Formation

TLDR
At low concentrations in the growth medium of persistently prion‐infected neuroblastoma cells, aptamer DP7 significantly reduced the relative proportion of de novo synthesized PK‐resistant PrPSc within only 16 h, opening the door towards a rational development of a new class of drugs for the therapy or prophylaxis of prion diseases.

Non-genetic propagation of strain-specific properties of scrapie prion protein

TLDR
Self-propagation of PrPSc polymers with distinct three-dimensional structures could be the molecular basis of scrapie strains, providing evidence that the protein-only model of infectious agents causing scrapie and other transmissible spon-giform encephalopathies is feasible.

Purification and properties of the cellular and scrapie hamster prion proteins.

TLDR
Development of a purification protocol for PrPC should facilitate comparisons of the two PrP isoforms and lead to an understanding of how PrPSc is synthesized either from PrPC or a precursor.

Strain-specific prion-protein conformation determined by metal ions

TLDR
It is shown that two different human PrPSc types, seen in clinically distinct subtypes of classical Creutzfeldt–Jakob disease, can be interconverted in vitro by altering their metal-ion occupancy and represents a new mechanism for post-translational modification of PrP.
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