Keywords: Disulfide Bond, Energy Landscape, Intermediate State, N-Terminal Domain, Prion-Susceptible Species, Octapeptide, Prion Protein, Article, Dielectric Constant, Enthalpy, Human, Nonhuman, Protein Analysis, Protein Folding, Protein Function, Protein Stability, Protein Structure, Simulation, Animals, Calorimetry, Differential Scanning, Disulfides Chemistry Metabolism, Molecular Dynamics Simulation, Mutation, Prions Chemistry Genetics Metabolism, Protein Isoforms, Protein Processing, Post-Translational, Spectrometry, Fluorescence,
Affiliations: *** IBB - CNR ***
Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati, Via Bonomea 265Trieste, Italy
Italian Institute of Technology, Scuola Internazionale Superiore di Studi Avanzati Unit, Via Bonomea 265Trieste, Italy
Department of Physics, Scuola Internazionale Superiore di Studi AvanzatiTrieste, Italy
National Research Council, Institute of Biostructures and Bioimaging, Viale Andrea Doria 6Catania, Italy
Elettra - Sincrotrone Trieste S.C.p.A., AREA Science ParkBasovizza Trieste, Italy
European Center for the Sustainable Impact of Nanotechnology, Veneto Nanotech S.C.p.A.Rovigo, Italy
Laboratory of Biochemistry, Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390Barcelona, Spain
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Prusiner, S. B., Prions (1998) Proc Natl Acad Sci USA, 95, pp. 13363-1338
Prusiner, S. B., Novel proteinaceous infectious particles cause scrapie (1982) Science, 216, pp. 136-144
Damberger, F. F., Christen, B., Perez, D. R., Hornemann, S., Wuthrich, K., Cellular prion protein conformation and function (2011) Proc Natl Acad Sci USA, 108, pp. 17308-17313
Hornshaw, M. P., McDermott, J. R., Candy, J. M., Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein (1995) BiochemBiophys Res Commun, 207, pp. 621-629
Brown, D. R., Hafiz, F., Glasssmith, L. L., Wong, B. S., Jones, I. M., Clive, C., Consequences of manganese replacement of copper for prion protein function and proteinase resistance (2000) EMBO J, 19, pp. 1180-1186
Jackson, G. S., Murray, I., Hosszu, L. L., Gibbs, N., Waltho, J. P., Clarke, A. R., Location and properties of metal-binding sites on the human prion protein (2001) Proc Natl Acad Sci USA, 98, pp. 8531-8535
Jones, C. E., Klewpatinond, M., Abdelraheim, S. R., Brown, D. R., Viles, J. H., Probing copper2+ binding to the prion protein using diamagnetic nickel2+ and 1H NMR: The unstructured N terminus facilitates the coordination of six copper2+ ions at physiological concentrations (2005) J Mol Biol, 346, pp. 1393-1407
Pan, K. M., Baldwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D., Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins (1993) Proc Natl Acad Sci USA, 90, pp. 10962-10966
Cohen, F. E., Prusiner, S. B., Pathologic conformations of prion proteins (1998) Annu Rev Biochem, 67, pp. 793-819
Hill, A. F., Antoniou, M., Collinge, J., Protease-resistant prion protein produced in vitro lacks detectable infectivity (1999) J Gen Virol, 80, pp. 11-14
Colby, D. W., Prusiner, S. B., Prions (2011) Cold Spring Harbor Perspect Biol, 3, p. a006833
McKinley, M. P., Bolton, D. C., Prusiner, S. B., A protease-resistant protein is a structural component of the scrapie prion (1983) Cell, 35, pp. 57-62
Zou, W. Q., Capellari, S., Parchi, P., Sy, M. S., Gambetti, P., Chen, S. G., Identification of novel proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt-Jakob disease (2003) J Biol Chem, 278, pp. 40429-40436
Colby, D. W., Giles, K., Legname, G., Wille, H., Baskakov, I. V., DeArmond, S. J., Design and construction of diverse mammalian prion strains (2009) Proc Natl Acad Sci USA, 106, pp. 20417-20422
Baskakov, I. V., Legname, G., Prusiner, S. B., Cohen, F. E., Folding of prion protein to its native alpha-helical conformation is under kinetic control (2001) J Biol Chem, 276, pp. 19687-19690
Palmer, M. S., Mahal, S. P., Campbell, T. A., Hill, A. F., Sidle, K. C., Laplanche, J. L., Deletions in the prion protein gene are not associated with CJD (1993) Hum Mol Genet, 2, pp. 541-544
Morrissey, M. P., Shakhnovich, E. I., Evidence for the role of PrP (C) helix 1 in the hydrophilic seeding of prion aggregates (1999) Proc Natl Acad Sci USA, 96, pp. 11293-11298
Speare, J. O., Rush, T. S., Bloom, M. E., Caughey, B., The role of helix 1 aspartates and salt bridges in the stability and conversion of prion protein (2003) J Biol Chem, 278, pp. 12522-12529
Chianini, F., Sis, S., Ricci, E., Eaton, S. L., Finlayson, J., Pang, Y., Pathogenesis of scrapie in ARQ/ARQ sheep after subcutaneous infection: Effect of lymphadenectomy and immune cell subset changes in relation to prion protein accumulation (2013) Vet Immunol Immunopathol, 152, pp. 348-358
Kiss, R. S., Ryan, R. O., Hicks, L. D., Oikawa, K., Kay, C. M., Physical properties of apolipoprotein A-I from the chicken, Gallus domesticus (1993) Biochemistry, 32, pp. 7872-7878
Maiti, N. R., Surewicz, W. K., The role of disulfide bridge in the folding and stability of the recombinant human prion protein (2001) J Biol Chem, 276, pp. 2427-2431
Jaffrey, S. R., Snyder, S. H., The biotin switch method for the detection of S-nitrosylated proteins (2001) Sci STKE, 2001, p. l1
McDonald, A. J., Millhauser, G. L., PrP overdrive: Does inhibition of alpha-cleavage contribute to PrP toxicity and prion disease? (2014) Prion, 8. , Epub 2014 Apr 10
Van Den Ent, F., L we, J., RF cloning: A restriction-free method for inserting target genes into plasmids (2006) J Biochem Biophys Methods, 67, pp. 67-74
Studier, F. W., Protein production by auto-induction in high density shaking cultures (2005) Protein Expression Purif, 41, pp. 207-234
Becktel, W. J., Schellman, J. A., Protein stability curves (1987) Biopolymers, 26, pp. 1859-1877
Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., Case, D. A., Development and testing of a general amber force field (2004) J Comput Chem, 25, pp. 1157-1174
Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., Klein, M. L., Comparison of simple potential functions for simulating liquid water (1983) J Chem Phys, 79, pp. 926-935
Nos, S., A molecular dynamics method for simulations in the canonical ensemble (2002) Mol Phys, 100, pp. 191-198
Hoover, W. G., Canonical dynamics: Equilibrium phase-space distributions (1985) Phys Rev A, 31, pp. 1695-1697
Biarn s, X., Pietrucci, F., Marinelli, F., Laio, A., METAGUI. A VMD interface for analyzing metadynamics and molecular dynamics simulations (2012) Comput Phys Commun, 183, pp. 203-211
No, F., Horenko, I., Sch tte, C., Smith, J., Hierarchical analysis of conformational dynamics in biomolecules: Transition networks of metastable states (2007) J Chem Phys, 126, p. 155102
Structural determinants in prion protein folding and stability
Prions are responsible for a heterogeneous group of fatal neurodegenerative diseases, involving post-translational modifications of the cellular prion protein. Epidemiological studies on Creutzfeldt-Jakob disease, a prototype prion disorder, show a majority of cases being sporadic, while the remaining occurrences are either genetic or iatrogenic. The molecular mechanisms by which PrPC is converted into its pathological isoform have not yet been established. While point mutations and seeds trigger the protein to cross the energy barriers, thus causing genetic and infectious transmissible spongiform encephalopathies, respectively, the mechanism responsible for sporadic forms remains unclear. Since prion diseases are protein-misfolding disorders, we investigated prion protein folding and stability as functions of different milieus. Using spectroscopic techniques and atomistic simulations, we dissected the contribution of major structural determinants, also defining the energy landscape of prion protein. In particular, we elucidated (i) the essential role of the octapeptide region in prion protein folding and stability, (ii) the presence of a very enthalpically stable intermediate in prion-susceptible species, and (iii) the role of the disulfide bridge in prion protein folding.
Structural determinants in prion protein folding and stability
No results.
Structural determinants in prion protein folding and stability