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The first demonstration that infectious prion particles could be generated in vitro by mixing uninfected and prion-infected brain homogenates in serial rounds of dilution and sonication. This method is now widely termed protein misfolding cyclic amplification, or PMCA.
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First NMR solution structure of the globular fold of PrP-sen.
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NMR solution structure of human prion protein
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Prion protein NMR structures of chickens, turtles, and frogs
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Haire L.F., Whyte S.M., Vasisht N., Gill A.C., Verma C., Dodson E.J., Dodson G.G., and Bayley P.M. The crystal structure of the globular domain of sheep prion protein. J Mol Biol 336 (2004) 1175-1183
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NMR structure of the bovine prion protein isolated from healthy calf brains
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This work showed that the three-dimensional structure of natural mammalian PrP and genetically engineered recombinant PrP are essentially the same, thus providing validation to the majority of structural studies which must rely on recombinant PrP.
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Hornemann S., Schorn C., and Wuthrich K. NMR structure of the bovine prion protein isolated from healthy calf brains. EMBO Rep 5 (2004) 1159-1164. This work showed that the three-dimensional structure of natural mammalian PrP and genetically engineered recombinant PrP are essentially the same, thus providing validation to the majority of structural studies which must rely on recombinant PrP.
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First definitive mapping study showing that it was the central region of the PrP primary amino acid sequence that influenced the species-specific conversion of PrP-sen to PrP-res.
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First demonstration that sequence homology at a single amino acid residue could determine whether or not conversion of PrP-sen to PrP-res was possible.
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Priola S.A., and Chesebro B. A single hamster amino acid blocks conversion to protease-resistant PrP in scrapie-infected mouse neuroblastoma cells. J Virol 69 (1995) 7754-7758. First demonstration that sequence homology at a single amino acid residue could determine whether or not conversion of PrP-sen to PrP-res was possible.
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Priola S.A., Chabry J., and Chan K. Efficient conversion of normal prion protein (PrP) by abnormal hamster PrP is determined by homology at amino acid residue 155. J Virol 75 (2001) 4673-4680
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First transmission electron microscopy images of scrapie-associated fibrils. The images were obtained before it was known that PrP-res was a major constituent of the fibrils.
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This study demonstrated that FTIR could be applied to the analysis of PrP-res aggregates.
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The author demonstrated that FTIR could be used to differentiate β-sheet conformation of PrP-res strains providing support for the hypothesis that prion strains are conformation-based.
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