In FY2013: 1) We have worked toward a better understanding of prion structure by initiating the application of new (to our lab) biochemical, immunological, spectroscopic, electron microscopic, and computational approaches to defining the structure of infectious prions. We have developed new models of prion structure is being built and evaluated based on our own new data, as well as published reports. These models are based on parallel-in-register beta sheet architectures, partial versions of which have been proposed by others. These developments are in progress and are expected to lead to significant discoveries soon. 2) We have assessed the role of normal prion protein in responses to stimulators of toll-like receptor ligands and have not found any significant effects. 3) We have probed the role of normal prion protein in the experimental autoimmune encephalomyelitis in mice of the C57/BL background and found no significant effect.

Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2013
Total Cost
$524,834
Indirect Cost
City
State
Country
Zip Code
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 :
Crowell, Jenna; Hughson, Andrew; Caughey, Byron et al. (2015) Host Determinants of Prion Strain Diversity Independent of Prion Protein Genotype. J Virol 89:10427-41
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
Groveman, Bradley R; Dolan, Michael A; Taubner, Lara M et al. (2014) Parallel in-register intermolecular beta sheet architectures for prion seeded PrP amyloids. J Biol Chem :
Kraus, Allison; Groveman, Bradley R; Caughey, Byron (2013) Prions and the potential transmissibility of protein misfolding diseases. Annu Rev Microbiol 67:543-64
Hasebe, Rie; Raymond, Gregory J; Horiuchi, Motohiro et al. (2012) Reaction of complement factors varies with prion strains in vitro and in vivo. Virology 423:205-13
Barton, Kelly A; Caughey, Byron (2011) Is PrP the road to ruin? EMBO J 30:1882-4
Smirnovas, Vytautas; Baron, Gerald S; Offerdahl, Danielle K et al. (2011) Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange. Nat Struct Mol Biol 18:504-6
Orru, Christina D; Wilham, Jason M; Raymond, Lynne D et al. (2011) Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. MBio 2:e00078-11

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