Abstract
The “protein-only” hypothesis (Alper et al., 1967; Griffith, 1967; Prusiner, 1982) states that the infectious agent of mammalian transmissible spongiform encephalopathies, such as Scrapie in sheep, bovine spongiform encephalopathy (BSE), and the Creutzfeldt-Jakob disease (CJD), the Gerstmann-Sträussler-Scheincker syndrome (GSS), fatal familial insomnia (FFI) and Kuru in man, is mainly, if not entirely, composed of a single protein, the “scrapie” form of the prion protein, PrPSc (Prusiner, 1982; Prusiner, 1991; Weissmann, 1994; Weissmann, 1996). This infectious form of the prion prtotein, PrP, is believed to be chemically identical to its monomeric, cellular form, PrPC (Stahl & Prusiner, 1991), but PrPSc appears to possess a different three-dimensional structure with increased β-sheet content (Pan et al., 1993) and forms oligomeric, protease-resistant aggregates (Prusiner, 1982; Bolton et al., 1982).
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References
Alper, T., Cramp, W. A., Haig, D. A., and Clarke, M. C., 1967, Does the agent of scrapie replicate without nucleic acid?, Nature 14:764–766.
Baldwin, R. L., 1996, On-pathway versus off-pathway folding intermediates, Folding & Design 1:R1–R8.
Bessen, R. A., Kocisko, D. A., Raymond, G. J., Nandan, S., Lansbury, P. T., and Caughey, B., 1995, Non-genetic propagation of strain-specific properties of scrapie prion protein, Nature 375:698–700.
Bolton, D. C., McKinley, M. P., and Prusiner, S. B., 1982, Identification of a protein that purifies with the scrapie prion, Science 218:1309–1311.
Büeler, H., Aguzzi, A., Sailer, A., Greiner, R. A., Autenried, P., Aguet, M., and Weissmann, C., 1993, Mice devoid of PrP are resistant to scrapie, Cell 73:1339–1347.
Collinge, J., Whittington, M. A., Sidle, K. C., Smith, C. J., Palmer, M. S., Clarke, A. R., and Jefferys, J. G. R., 1994, Prion protein is necessary for normal synaptic function, Nature 370:295–297.
Cornell, W. D., Cieplak, P., Bayly, C. L, Gould, I. R., Merz Jr., K. M., Ferguson, D. M., Spellmeyer, D. C., Fox, T., Caldwell, J. W., and Kollmam, P. A., 1995, A second generation force field for the simulation of proteins, nucleic acids, and organic molecules, J. Am. Chem. Soc. 117:5179–5197.
Fischer, M., Rülicke, T., Raeber, A., Sailer, A., Moser, M., Oesch, B., Brandner, S., Aguzzi, A., and Weissmann, C., 1996, Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie, EMBO J. 15:1255–1264.
Goldfarb, L. G., Petersen, R. B., Tabaton, M., Brown, P., LeBlanc, A. C., Montagna, P., Cortelli, P., Julien, J., Vital., C., Pendelbury, W. W., Haltia, M., Wills, P. R., Hauw, J. J., McKeever, P. E., Monari, L., Schrank, B., Swergold, G. D., Autilio-Gambetti, L., Gajdusek, D. C., Lugaresi, E., and Gambetti, P., 1992, Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Disease phenotype determined by a DNA polymorphism, Science 258: 806–808.
Griffith, J. S., 1967, Self-replication and scrapie, Nature 215:1043–1044.
Güntert, P., Braun, W., and Wüthrich, K., 1991, Efficient computation of three-dimensional protein structures in solution from nuclear magnetic resonance data using the program DIANA and the supporting programs CALIBA, HABAS and GLOMSA, J. Mol Biol. 217:517–530.
Holm, L. and Sander, C., 1994, Protein structure comparison by alignment of distance matrices, J. Mol Biol 233:123–138.
Honig, B. and Nicholls, A., 1994, Classical electrostatics in biology and chemistry, Science 268:1144–1149.
Hornemann, S. and Glockshuber, R., 1996, Autonomous and reversible folding of a soluble amino-terminally truncated segment of the mouse prion protein, J. Mol Biol 261:614–619.
Hsiao, K., Baker, H. F., Crow, T. J., Poulter, M., Owen, F., Terwilliger, J. D., Westaway, D., Ott, J., and Prusiner, S. B., 1989, Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome, Nature 338:342–345.
Huang, Z., Gabriel, J.-M., Baldwin, M. A., Fletterick, R. J., Prusiner, S. B., and Cohen, F. E., 1994, Proposed three-dimensional structure for the cellular prion protein, Proc. Natl Acad. Sci, U.S.A. 91:7139–7143.
Huang, Z., Prusiner S. B. & Cohen, F. E., 1995, Scrapie prions: a three-dimensional model of an infectious fragment, Folding & Design 1:13–19.
Jarrett, J. T. and Lansbury Jr., P. T., 1993, Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie? Cell 73:1055–1058.
Johnson Jr., W. C., 1990, Protein secondary structure and circular dichroism: A practical guide, Proteins: Struct. Funct. Genet. 7:205–214.
Koradi, R., Billeter, M., and Wüthrich, K., 1996, MOLMOL: a program for display and analysis of macromolecular structures, J. Mol Graph. 14: 51–55 (1996).
Lledo, P.-M., Tremblay, P., DeArmond, S.J., Prusiner, S. B., and Nicoll, R. A., 1996, Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the hippocampus, Proc. Natl. Acad. Sci. U.S.A. 93:2403–2407.
Luginbühl, P., Güntert, P., Billeter, M., and Wüthrich, K., 1996, The new program OPAL for molecular dynamics simulations and energy refinements of biological macromolecules, J. Biomol. NMR 8:136–146.
Mehlhorn, I., Groth, D., Stöckel, J., Moffat, B., Reilly, D., Yansura, D., Willett, W.S., Baldwin, M., Fletterick, R., Cohen, F. E., Vandlen, R., Henner, D., and Prusiner, S. B., 1996, High-level expression and characterization of a purified 142 residue polypeptide of the prion protein, Biochemistry 35:5528–5537.
Myers, J. K., Pace, C. N. & Scholtz, J. M., 1995, Denaturant m values and heat capacity changes: Relation to changes in accessible surface areas of protein unfolding, Protein Sci. 4:2138–2148.
Palmer, M. S., Dryden, A. J., Hughes, J. T., and Collinge, J., 1991, Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease, Nature 352:340–342.
Pan, K.-M., Baldwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D., Mehlhorn, I., Huang, Z., Fletterick, R. J., Cohen, F. E., and Prusiner, S. B., 1993, Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins, Proc. Natl Acad. Sci., U.S.A. 90:10962–10966.
Price, N. C. and Johnson, C. M., 1993, Proteinases as probes of conformation of soluble proteins. In Proteolytic Enzymes, A Practical Approach (Beynon, R. J. & Bond, J. S., eds.), pp. 163–180, IRL Press, Oxford.
Prusiner, S. B., 1982, Novel proteinaceous infectious particles cause scrapie, Science 216:136–144.
Prusiner, S. B., 1991, Molecular biology of prion diseases, Science 252:1515–1522.
Prusiner, S. B., 1993, Genetic and infectious prion diseases, Arch. Neurol. 50:1129–1153.
Prusiner, S. B., Groth, D., Serban, A., Stahl, N., and Gabizon, R., 1993, Attempts to restore scrapie infectivity after exposure to protein denaturants, Proc. Natl Acad. Sci. U.S.A. 90:2793–2797.
Riek, R., Hornemann, S., Wider, G., Billeter, M., Glockshuber, R., and Wüthrich, K., 1996, NMR structure of the mouse prion protein domain PrP(121–231), Nature 382:180–182.
Santoro, M. M. and Bolen, D. W., 1988, Unfolding free energy changes determined by the linear extrapolation method. 1. Unfolding of phenylmethanesulfonyl a-chymotrypsin using different denaturants, Biochemistry 27:8063–8068.
Sakaguchi, S., Katamine, S., Nishida, N., Moriuchi, R., Shigematsu, K., Sugimoto, T., Nakatani, A., Katoaka, Y., Houtani, T., Shirabe, S., Okada, H., Hasegawa, S., Miyamoto, T., and Noda, T., 1996, Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene, Nature 380:528–531.
Schätzl, H. M., Da Costa, M., Taylor, L., Cohen F. E., and Prusiner, S. B., 1995, Prion protein gene variation among primates, J. Mol. Biol. 245:362–374.
Scott, M., Groth, D., Foster, D., Torchia, M., Yang, S-L., DeArmond, S. J., and Prusiner, S. B., 1993, Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes, Cell 73:979–988.
Stahl, N. and Prusiner S. B., 1991, Prions and prion proteins. FASEB J. 5:2799–2807.
Studier, F. W. and Moffatt, B. A., 1986, Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes, J. Mol Biol. 189:113–130.
Telling, G. C., Scott, M., Mastrianni, J., Gabizon, R., Torchia, M., Cohen, F. E., DeArmond, S. J., and Prusiner, S. B., 1995, Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein, Cell 83:79–90.
Tobler, I., Gaus, S. E., Deboer, T., Achermann, P., Fischer, M., Rülicke, T., Moser, M., Oesch, B., McBride, P. A., and Manson, J. C., 1996, Altered circadian activity rhythms and sleep in mice devoid of prion protein, Nature 380:639–642.
Weissmann, C., 1994, Molecular biology of prion diseases, Trends Cell Biol. 4:10–14.
Weissmann, C., 1996, Molecular biology of transmissible spongiform encephalopathies, FEBS Lett. 398:3–11.
Westaway, D., Goodman, P. A., Mirenda, C. A., McKinely, M.P., Carlson, G. A., and Prusiner, S. B., 1987, Distinct prion proteins in short and long scrapie incubation period mice, Cell 51:651–662.
Wüthrich, K., 1986, NMR of Proteins and Nucleic Acids, Wiley, New York.
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Glockshuber, R., Hornemann, S., Riek, R., Wider, G., Billeter, M., Wüthrich, K. (1998). Autonomous Folding and Three-Dimensional Structure of the Carboxy-Terminal Domain of the Mouse Prion Protein, PrP(121–231). In: Morrison, D.R.O. (eds) Prions and Brain Diseases in Animals and Humans. NATO ASI Series, vol 295. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1896-3_21
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