Abstract

The structure of the infectious form of prion protein, PrPSc, remains unclear. One recent approach to solving protein amyloid fibril structures is cryo-electron microscopy, which has recently been used by other groups to reveal the amyloid core structures of disease-associated tau and synuclein fibrils. We have begun to pursue cryo-electron microscopy-based elucidation of PrPSc structure. Progress has been made, with lateral views and image reconstructions revealing stacked beta sheets running perpendicular to the fibril axis. The spacing between the sheets is 4.8 A. However, so far the resolution obtained has been insufficient to decipher the backbone folding of the core of amyloid fibrils of brain-derived PrPSc.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI000580-30
Application #
10014041
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
30
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Cracco, Laura; Notari, Silvio; Cali, Ignazio et al. (2017) Novel strain properties distinguishing sporadic prion diseases sharing prion protein genotype and prion type. Sci Rep 7:38280
Wang, Fei; Wang, Xinhe; Orrú, Christina D et al. (2017) Self-propagating, protease-resistant, recombinant prion protein conformers with or without in vivo pathogenicity. PLoS Pathog 13:e1006491
Bett, Cyrus; Lawrence, Jessica; Kurt, Timothy D et al. (2017) Enhanced neuroinvasion by smaller, soluble prions. Acta Neuropathol Commun 5:32
Groveman, Bradley R; Raymond, Gregory J; Campbell, Katrina J et al. (2017) Role of the central lysine cluster and scrapie templating in the transmissibility of synthetic prion protein aggregates. PLoS Pathog 13:e1006623
Kraus, Allison; Raymond, Gregory J; Race, Brent et al. (2017) PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions. J Virol 91:
Hughson, Andrew G; Race, Brent; Kraus, Allison et al. (2016) Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid. PLoS Pathog 12:e1005914
Alibhai, James; Blanco, Richard A; Barria, Marcelo A et al. (2016) Distribution of Misfolded Prion Protein Seeding Activity Alone Does Not Predict Regions of Neurodegeneration. PLoS Biol 14:e1002579
Saijo, Eri; Hughson, Andrew G; Raymond, Gregory J et al. (2016) PrPSc-Specific Antibody Reveals C-Terminal Conformational Differences between Prion Strains. J Virol 90:4905-13
Kraus, Allison; Anson, Kelsie J; Raymond, Lynne D et al. (2015) Prion Protein Prolines 102 and 105 and the Surrounding Lysine Cluster Impede Amyloid Formation. J Biol Chem 290:21510-22
Groveman, Bradley R; Kraus, Allison; Raymond, Lynne D et al. (2015) Charge neutralization of the central lysine cluster in prion protein (PrP) promotes PrP(Sc)-like folding of recombinant PrP amyloids. J Biol Chem 290:1119-28

Showing the most recent 10 out of 22 publications