Advertisement

The Generic Nature of Protein Folding and Misfolding

  • Christopher M. Dobson
Chapter
Part of the Protein Reviews book series (PRON, volume 4)

Abstract

The ability of proteins to fold to their functional states is an astonishing example of the power of biological evolution at the molecular level. Despite the large number of different native protein folds, the process of folding can be described in terms of a universal mechanism that appears to be based on the generation of the correct overall topology through interactions involving a relatively small number of residues. Protein misfolding is an intrinsic aspect of normal folding within the complex cellular environment, and its effects are minimized in living systems by the action of a range of protective mechanisms including molecular chaperones and quality control systems. Unfolded and misfolded proteins have a tendency to aggregate to form a variety of species including the highly organized and kinetically stable amyloid fibrils. The latter species represent a generic form of structure resulting from the inherent polymer properties of polypeptide chains, and their formation is associated with a wide range of debilitating human diseases. Amyloid fibrils and their precursors appear to have similar adverse effects on cellular function regardless of the sequence of the component peptide or protein. Our increasing knowledge of the interplay between different forms of protein structure and their generic characteristics provides a platform for rational therapeutic intervention designed to prevent or treat this whole family of diseases.

Keywords

Polypeptide Chain Molecular Chaperone Prion Protein Amyloid Deposit Prion Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Balbach, J., and Schmid, F.X. (2000). Proline isomerization and its catalysis in protein folding. In: Pain, R.H. (Ed.), Protein folding, 2nd ed. Oxford: Oxford University Press, pp. 212–249.Google Scholar
  2. Ban, T., Hamada, D., Hasegawa, K., Naiki, H., and Goto, Y. (2003). Direct observation of amyloid fibril growth monitored by thioflavin T fluorescence. J. Biol. Chem. 278:16462–16465.PubMedCrossRefGoogle Scholar
  3. Bence, N.F., Sampat, R.M., and Kopito, R.R. (2001). Impairment of the ubiquitin-proteosome system by protein aggregation. Science 292:1552–1555.PubMedCrossRefGoogle Scholar
  4. Bitan, G., Kirkitadze, M.D., Lomakin, A., Vollers, S.S., Benedek, G.B., and Teplow, D.B. (2003). Amyloid beta-protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways. Proc. Natl. Acad. Sci. USA 100:330–335.PubMedCrossRefGoogle Scholar
  5. Booth, D.R., Sunde, M., Bellotti, V., Robinson, C.V., Hutchinson, W.L., Fraser, P.E., Hawkins, P.N., Dobson, C.M., Radford, S.E., Blake, C.C.F., and Pepys, M.B. (1997). Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 385:787–793.PubMedCrossRefGoogle Scholar
  6. Bouchard, M., Zurdo, J., Nettleton, E.J., Dobson, C.M., and Robinson, C.V. (2000). Formation of insulin amyloid fibrils followed by FTIR simultaneously with CD and electron microscopy. Protein Sci. 9:1960–1967.PubMedGoogle Scholar
  7. Branden, C., and Tooze, J. (1999). Introduction to protein structure. 2nd ed. New York: Garland Publishing.Google Scholar
  8. Broome, B.M., and Hecht, M.H. (2000). Nature disfavours sequences of alternating polar and non-polar amino acids: implications for amyloidogenesis. J. Mol. Biol. 296:961–968.PubMedCrossRefGoogle Scholar
  9. Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C.M., and Stefani, M. (2002). Inherent cytotoxicity of aggregates implies a common origin for protein misfolding diseases. Nature 416:507–511.PubMedCrossRefGoogle Scholar
  10. Bucciantini, M., Calloni, G., Chiti, F., Formighi, L., Nosi, D., Dobson, C.M., and Stefani, M. (2004). Pre-fibrillar amyloid protein aggregates share common features of cytotoxicity. J. Biol. Chem. 279:31374–31382.PubMedCrossRefGoogle Scholar
  11. Capaldi, A.P., Kleanthous, C., and Radford, S.E. (2002). Im7 folding mechanism: misfolding on a path to the native state. Nat. Struct. Biol. 9:209–216.PubMedGoogle Scholar
  12. Caughey, B., and Lansbury, P.T., Jr. (2003). Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu. Rev. Neurosci. 26:267–298.PubMedCrossRefGoogle Scholar
  13. Chamberlain, A.K., MacPhee, C.E., Zurdo, J., Morozova-Roche, L.A., Hill, H.A., Dobson, C.M., and Davis, J.J. (2000). Ultrastructural organisation of amyloid fibrils by atomic force microscopy. Biophys. J. 79:3282–3293.PubMedGoogle Scholar
  14. Cheung, M.S., Garcia, A.E., and Onuchic, J.N. (2002). Protein folding mediated by solvation: water expulsion and formation of the hydrophobic core occur after the structural collapse. Proc. Natl. Acad. Sci. USA 99:685–690.PubMedCrossRefGoogle Scholar
  15. Chien, P., DePace, A.H., Collins, S.R., and Weissman, J.S. (2003). Generation of prion transmission barriers by mutational control of amyloid conformations. Nature 424:948–951.PubMedCrossRefGoogle Scholar
  16. Chien, P., Weismann, J.S., and DePace, A.H. (2004). Emerging principles of conformation-based prion inheritance. Annu. Rev. Bio Chem. 73:617–656.CrossRefGoogle Scholar
  17. Chiti, F., Webster, P., Taddei, N., Clark, A., Stefani, M., Ramponi, G., and Dobson, C.M. (1999). Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc. Natl. Acad. Sci. USA 96:3590–3594.PubMedCrossRefGoogle Scholar
  18. Chiti, F., Taddei, N., Baroni, F., Capanni, C., Stefani, M., Ramponi, G., and Dobson, C.M. (2002). Kinetic partitioning of protein folding and aggregation. Nat. Struct. Biol. 9:137–143.PubMedCrossRefGoogle Scholar
  19. Chiti, F., Stefani, M., Taddei, N., Ramponi, G., and Dobson, C.M. (2003). Rationalisation of mutational effects on peptide and protein aggregation rates. Nature 424:805–808.PubMedCrossRefGoogle Scholar
  20. Cohen, F.E., and Kelly, J.W. (2003). Therapeutic approaches to protein-misfolding diseases. Nature 426:905–909.PubMedCrossRefGoogle Scholar
  21. Csermely, P. (2001). Chaperone overload is a possible contributor to “civilization diseases.” Trends Gen. 17:701–704.CrossRefGoogle Scholar
  22. Davis, R., Dobson, C.M., and Vendruscolo, M. (2002). Determination of the structures of distinct transition state ensembles for a β-sheet peptide with parallel folding pathways. J. Chem. Phys. 117:9510–9517.CrossRefGoogle Scholar
  23. Debe, D.A., Carlson, M.J., and Goddard, W.A., III. (1999). The topomer-sampling model of protein folding. Proc. Natl. Acad. Sci. USA 96:2596–2601.PubMedCrossRefGoogle Scholar
  24. Dill, K.A., and Chan, H.S. (1997). From Levinthal to pathways to funnels. Nat. Struct. Biol. 4:10–19.PubMedCrossRefGoogle Scholar
  25. Dobson, C.M. (1999). Protein misfolding, evolution and disease. Trends Biochem. Sci. 24:329–332.PubMedCrossRefGoogle Scholar
  26. Dobson, C.M. (2001). The structural basis of protein folding and its links with human disease. Philos. Trans. R. Soc. Lond. B 356:133–145.CrossRefGoogle Scholar
  27. Dobson, C.M. (2002). Getting out of shape—protein misfolding diseases. Nature 418:729–730.PubMedCrossRefGoogle Scholar
  28. Dobson, C.M. (2003). Protein folding and misfolding. Nature 426:884–890.PubMedCrossRefGoogle Scholar
  29. Dobson, C.M. (2004a). In the footsteps of alchemists. Science 295:1719–1722.Google Scholar
  30. Dobson, C.M. (2004b). Principles of protein folding, misfolding and aggregation. Semin. Cell Dev. Biol. 15:3–16.PubMedCrossRefGoogle Scholar
  31. Dobson, C.M., and Karplus, M. (1999). The fundamentals of protein folding: bringing together theory and experiment. Curr. Opin. Struct. Biol. 9:92–101.PubMedCrossRefGoogle Scholar
  32. Dobson, C.M., Sali, A., and Karplus, M. (1998). Protein folding: a perspective from theory and experiment. Angew. Chem. Int. Ed. Eng. 37:868–893.CrossRefGoogle Scholar
  33. DuBay, K.F., Pawar, A.P., Chiti, F., Zurdo, J., Dobson, C.M., and Vendruscolo, M. (2004). Prediction of the absolute aggregation rates of amyloidogenic polypeptide chains. J. Mol. Biol. 341:1317–1326.PubMedCrossRefGoogle Scholar
  34. Dumoulin, M., and Dobson, C.M. (2005). Probing the origins, diagnosis and treatment of amyloid disease using antibodies. Biochimie. 86:589–600.CrossRefGoogle Scholar
  35. Dumoulin, M., Last, A.M., Desmyter, A., Decanniere, K., Canet, D., Spencer, A., Archer, D.B., Muyldermans, S., Wyns, L., Matagne, A., Redfield, C., Robinson, C.V., and Dobson, C.M. (2003). A camelid antibody fragment inhibits amyloid fibril formation by human lysozyme. Nature 424:783–788.PubMedCrossRefGoogle Scholar
  36. Ellis, R.J. (Ed.). (1996). The chaperonins. San Diego, CA: Academic Press.Google Scholar
  37. Ellis, R.J., and Hartl, F.U. (1999). Principles of protein folding in the cellular environment. Curr. Opin. Struct. Biol. 9:102–110.PubMedCrossRefGoogle Scholar
  38. Ellis, R.J., and Minton, A.P. (2003). Join the crowd. Nature 425:27–28.PubMedCrossRefGoogle Scholar
  39. Fändrich, M., and Dobson, C.M. (2002). The behaviour of polyamino acids reveals an inverse side-chain effect in amyloid structure formation. EMBO J. 21:5682–5690.PubMedCrossRefGoogle Scholar
  40. Fändrich, M., Fletcher, M.A., and Dobson, C.M. (2001). Amyloid fibrils from muscle myoglobin. Nature 410:165–166.PubMedCrossRefGoogle Scholar
  41. Fersht, A.R. (1999). Structure and mechanism in protein science: a guide to enzyme catalysis and protein folding. New York: W.H. Freeman.Google Scholar
  42. Fersht, A.R. (2000). Transition-state structure as a unifying basis in protein-folding mechanisms: contact order, chain topology, stability, and the extended nucleus mechanism. Proc. Natl. Acad. Sci. USA 97:1525–1529.PubMedCrossRefGoogle Scholar
  43. Fersht, A.R. and Daggett, V. (2002). Protein folding and unfolding at atomic resolution. Cell 108:573–582.PubMedCrossRefGoogle Scholar
  44. Gejyo, F., Homma, N., Suzuki, Y., and Arakawa, M. (1986). Serum levels of β2-microglobulin as a new form of amyloid protein in patients undergoing long-term hemodialysis. N. Engl. J. Med. 314:585–586.PubMedCrossRefGoogle Scholar
  45. Gilbert, R.J.C, Fucini, P., Connell, S., Fuller, S.D., Nierhaus, K.H., Robinson, C.V., Dobson, C.M., and Stuart, D.I. (2004). Three-dimensional structures of translating ribosomes by cryo-EM. Mol. Cell. 14:57–66.PubMedCrossRefGoogle Scholar
  46. Hammarstrom, P., Wiseman, R.L., Powers, E.T., and Kelly, J.W. (2003). Prevention of transthyretin amyloid disease by changing protein misfolding energetics. Science 299:713–716.PubMedCrossRefGoogle Scholar
  47. Hardesty, B., and Kramer, G. (2001). Folding of a nascent peptide on the ribosome. Prog. Nucleic Acid Res. Mol. Biol. 66:41–66.PubMedGoogle Scholar
  48. Harper, J.D., and Lansbury, P.T., Jr. (1997). Models of amyloid seeding in Alzheimer’s disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu. Rev. Bioi Chem. 66:385–407.CrossRefGoogle Scholar
  49. Hartl, F.U., and Hayer-Hartl, M. (2002). Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858.PubMedCrossRefGoogle Scholar
  50. Höppener, J.W.M., Nieuwenhuis, M.G., Vroom, T.M., Ahrén, B., and Lips, C.J.M. (2002). Role of islet amyloid in type 2 diabetes mellitus: consequence or cause? Mol. Cell. Endocrinol. 197:205–212.PubMedCrossRefGoogle Scholar
  51. Hore, P.J., Winder, S.L., Roberts, C.H., and Dobson, C.M. (1997). Stopped-flow photo-CIDNP observation of protein folding. J. Am. Chem. Soc. 119:5049–5050.CrossRefGoogle Scholar
  52. Horwich, A. (2002). Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions. J. Clin Invest. 110:1221–1232.PubMedCrossRefGoogle Scholar
  53. Jackson, S.E. (1998). How do small single-domain proteins fold? Fold. Des. 3:R81–R91.PubMedCrossRefGoogle Scholar
  54. Jaroniec, C.P., MacPhee, C.E., Bajaj, V.S., McMahon, M.T., Dobson, C.M., and Griffin, R.G. (2004). High resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy. Proc. Natl. Acad. Sci. USA 101:711–716.PubMedCrossRefGoogle Scholar
  55. Jenni, S., and Ban, N. (2003). The chemistry of protein synthesis and voyage through the ribosomal tunnel. Curr. Opin. Struct. Biol. 13:212–219.PubMedCrossRefGoogle Scholar
  56. Jiménez, J.L., Guijarro, J.I., Orlova, E., Zurdo, J., Dobson, C.M., Sunde, M. and Saibil, H.R. (1999). Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. EMBO J. 18:815–821.PubMedCrossRefGoogle Scholar
  57. Jiménez, J.L., Nettleton, E.J., Bouchard, M., Robinson, C.V., Dobson, C.M., and Saibil, H.R. (2002). The protofilament structure of insulin amyloid fibrils. Proc. Natl. Acad. Sci. USA 99:9196–9201.PubMedCrossRefGoogle Scholar
  58. Karplus, M. (1997). The Levinthal paradox, yesterday and today. Fold. Des. 2:569–576.CrossRefGoogle Scholar
  59. Karplus, M., and Weaver, D.L. (1994). Folding dynamics: the diffusion-collision model and experimental data. Protein Sci. 3:650.PubMedCrossRefGoogle Scholar
  60. Kaufman, R.J. (2002). The unfolded protein response in nutrient sensing and differentiation. Nat. Rev. Mol. Cell Biol. 3:411–421.PubMedCrossRefGoogle Scholar
  61. Kayed, R., Head, E., Thompson, J.L., McIntire, T.M., Milton, S.C., Cotman, C.W., and Glabe, C.G. (2003). Common structure of soluble amyloid oligomers implies common mechanisms of pathogenesis. Science 300:486–489.PubMedCrossRefGoogle Scholar
  62. Kelly, J. (1998). Alternative conformation of amyloidogenic proteins and their multi-step assembly pathways. Curr. Opin. Struct. Biol. 8:101–106.PubMedCrossRefGoogle Scholar
  63. Klunk, W.E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., et al. (2004). Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann. Neurol. 55:306–319.PubMedCrossRefGoogle Scholar
  64. Koo, E.H., Lansbury, P.T., Jr., and Kelly, J.W. (1999). Amyloid diseases: abnormal protein aggregation in neurodegeneration. Proc. Natl. Acad. Sci. USA 96:9989–9990.PubMedCrossRefGoogle Scholar
  65. Korzhnev, D.M., Salvatella, X., Vendruscolo, M., Di Nardo, A.A., Davidson, A.R., Dobson, C.M., and Kay, L.E. (2004). Low populated folding intermediates of the Fyn SH3 domain characterized by relaxation dispersion NMR. Nature 430:586–590.PubMedCrossRefGoogle Scholar
  66. Krebs, M.R.H, MacPhee, C.E., Miller, A.F., Dunlop, I.E., Dobson, C.M., and Donald, A.M. (2004). The formation of spherulites by amyloid fibrils of bovine insulin. Proc. Natl. Acad. Sci. USA 101:14420–14424.PubMedCrossRefGoogle Scholar
  67. Lashuel, H.A., Hartley, D., Petre, B.M., Walz, T., Lansbury, P.T., Jr. (2002). Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 418:291.PubMedCrossRefGoogle Scholar
  68. Legname, G., Baskakov, I.V., Nguyen, H.O., Riesner, D., Cohen, F.E., DeArmond, S.J., and Prusiner, S.J. (2004). Synthetic mammalian prions. Science 305:673–676.PubMedCrossRefGoogle Scholar
  69. Lindorff-Larsen, K., Vendruscolo, M., Paci, E., and Dobson, C.M. (2004). Transition states for protein folding have native topologies despite high structural variability. Nat. Struct. Mol. Biol. 11:443–439.PubMedCrossRefGoogle Scholar
  70. Lopez de la Paz, M., Goldie, K., Zurdo, J., Lacrois, E., Dobson, C.M., Hoenger, A., and Serrano, L. (2002). De novo designed peptide-based amyloid fibrils. Proc. Natl. Acad. Sci. USA 99:16052–16057.PubMedCrossRefGoogle Scholar
  71. Macario, A.J.L., and de Macario, E.C. (2002). Sick chaperones and ageing: a perspective. Ageing Res. Rev. 1:295–311.PubMedCrossRefGoogle Scholar
  72. Makarov, D.E., and Plaxco, K.W. (2003). The topomer search model: a simple, quantitative theory of two-state protein folding kinetics. Protein Sci. 12:17–26.PubMedCrossRefGoogle Scholar
  73. Malisauskas, M., Zamotin, V., Jass, J., Noppe, W., Dobson, C.M., and Morozova-Roche, L.A. (2003). Amyloid protofilaments from the calcium-binding protein equine lysozyme: formation of ring and linear structures depends on pH and metal ion concentration. J. Mol. Biol. 330:879–890.PubMedCrossRefGoogle Scholar
  74. Matouschek, A., Kellis, J.T., Jr., Serrano, L., and Fersht, A.R. 1989. Mapping the transition state and pathway of protein folding by protein engineering. Nature 342:122.CrossRefGoogle Scholar
  75. May, B.C., Fafarman, A.T., Hong, S.B., Rogers, M., Deady, L.W., Prusiner, S.B., and Cohen, F.E. (2003). Potent inhibition of scrapie prion replication in cultured cells by bisacridines. Proc. Natl. Acad. Sci. USA 100:3416–3421.PubMedCrossRefGoogle Scholar
  76. Miller, M.W., and Williams, E.S. (2003). Horizontal prion transmission in male deer. Nature 425:35–36.PubMedCrossRefGoogle Scholar
  77. Muchowski, P.J., Schaffar, G., Sittler, A., Wanker, E.E., Hayer-Hartl, M.K., and Hartl, F.U. (2000). Hsp70 and Hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc. Natl. Acad. Sci. USA 97:7841–7846.PubMedCrossRefGoogle Scholar
  78. Nettleton, E.J., Tito, P., Sunde, M., Bouchard, M., Dobson, C.M., and Robinson, C.V. (2000). Characterization of the oligomeric states of insulin in self-assembly and amyloid fibril formation by mass spectrometry. Biophys. J. 79:1053–1065.PubMedCrossRefGoogle Scholar
  79. O’Nuallain, B., and Wetzel, B. (2002). Conformational Abs recognizing a generic amyloid fibril epitope. Proc. Natl. Acad. Sci. USA 99:1485–1490.PubMedCrossRefGoogle Scholar
  80. Paci, E., Friel, C., Lindorff-Larsen, K., Radford, S., Karplus, M., and Vendruscolo, M. (2004). Comparison of the transition states ensembles for folding of Im7 and Im9 determined using all-atom molecular dynamics simulations with Ф value restraints. Proteins 54:513–525.PubMedCrossRefGoogle Scholar
  81. Padrick, S.B., and Miranker, A.D. (2002). Islet amyloid phase partitioning and secondary nucleation are central to the mechanism of fibrillogenesis. Biochemistry 41:4694–4703.PubMedCrossRefGoogle Scholar
  82. Panchenko, A.R., Luthey-Schulter, Z., and Wolynes, P.G. (1996). Foldons, protein structureal modules, and exons. Proc. Natl. Acad. Sci. USA 93:2008–2013.PubMedCrossRefGoogle Scholar
  83. Pelham, H.R. 1986. Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell 46:959–961.PubMedCrossRefGoogle Scholar
  84. Pepys, M.B. (1995). Amyloidosis. In: Weatherall, D.J., Ledingham, J.G.G., and Warrell, D.A. (Eds.). The Oxford textbook of medicine, 3rd ed. Oxford: Oxford University Press, pp.1512–1524.Google Scholar
  85. Pepys, M.B., et al. (2002). Targeted pharmocological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 417:254–259.PubMedCrossRefGoogle Scholar
  86. Petkova, A.T., Ishii, Y., Balbach, J.J., Antzutkin, O.N., Leapman, R.D., Delaglio, F., and Tycko, R. (2002). A structural model for Alzheimer’s β-amyloid fibrils based on experimental constraints from solid state NMR. Proc. Natl. Acad. Sci. USA 99:16742–16747.PubMedCrossRefGoogle Scholar
  87. Plakoutsi, G., Taddei, N., Stefani, M., and Chiti, F. (2004). Aggregation of the acylphosphatase from sulfolobus solfataricus: the folded and partially unfolded states can both be precursors for amyloid formation. J. Biol. Chem. 279:14111–14119.PubMedCrossRefGoogle Scholar
  88. Polverino de Laureto, P., Taddei, N., Frare, E., Capanni, C., Constantini, S., Zurdo, J., Chiti, F., Dobson, C.M., and Fontana, A. (2003). Protein aggregatin and amyloid fibril formation by an SH3 domain probed by limited proteolysis. J. Mol. Biol. 334:129–141.PubMedCrossRefGoogle Scholar
  89. Prusiner, S. (1997). Prion diseases and the BSE crisis. Science 278:245–251.PubMedCrossRefGoogle Scholar
  90. Ramirez-Alvarado, M., Merkel, J.S., and Regan, L. (2000). A systematic exploration of the influence of the protein stability on amyloid fibril formation in vitro. Proc. Natl. Acad. Sci. USA 97:8979–8984.PubMedCrossRefGoogle Scholar
  91. Richardson, J.S., and Richardson, D.C. (2002). Natural β-sheet proteins use negative design to avoid edge-to-edge aggregation. Proc. Natl. Acad. Sci. USA 99:2754–2759.PubMedCrossRefGoogle Scholar
  92. Rousseau, F., Schymkowitz, J.W., Wilkinson, H.R., and Itzhaki, L.S. (2004). Intermediates control domain swapping during folding of p13suc1. J. Biol. Chem. 279:8368–8377.PubMedCrossRefGoogle Scholar
  93. Schenck, D. (2002). Amyloid-β immunotherapy for Alzheimer’s disease: the end of the beginning. Nat. Rev. Neurosci. 3:824–828.CrossRefGoogle Scholar
  94. Schiene, C., and Fisher, G. (2000). Enzymes that catalyse the restructuring of proteins. Curr. Opin. Struct. Biol. 10:40.PubMedCrossRefGoogle Scholar
  95. Schlunegger, M.P., Bennett, M.J., and Eisenberg, D. (1997). Oligomer formation by 3D domain swapping: a model for protein assembly and misassembly. Adv. Protein Chem. 50:61–122.PubMedGoogle Scholar
  96. Schubert, U., Anton, L.C., Gibbs, J., Orbyry, C.C., Yewdell, J.W., and Bennink, J.R. (2000). Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404:770–774.PubMedCrossRefGoogle Scholar
  97. Selkoe, D.J. (2003). Folding proteins in fatal ways. Nature 426:900–904.PubMedCrossRefGoogle Scholar
  98. Serpell, L.C, Blake, C.C.F., and Fraser, P.E. (2000). Molecular structure of a fibrillar Alzheimer’s Aß fragment. Biochemistry 39:13269–13275.PubMedCrossRefGoogle Scholar
  99. Sherman, M.Y., and Goldberg, A.L. (2001). Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29:15–32.PubMedCrossRefGoogle Scholar
  100. Shorter, J., and Lindquist, S. (2004). Hsp104 catalyzes formation and elimination of self-replicating Sup35 pion conformers. Science 304:1793–1797.PubMedCrossRefGoogle Scholar
  101. Sitia, R., and Braakman, I. (2003). Quality control in the endoplasmic reticulum folding factory. Nature 426:891–894.PubMedCrossRefGoogle Scholar
  102. Soto, C. (2003). Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. Neurosci. 4:49–60.PubMedCrossRefGoogle Scholar
  103. Stangou, A.J., Hawkins, P.N., Booth, D.R., O’Grady, J., Jewitt, D., Rela, M., Pepys, M.B., and Heaton, N.D. (1999). Liver transplantation for non-Met30 TTR associated familial amyloid polyneuropathy. Hepatology 30:576.CrossRefGoogle Scholar
  104. Stefani, M., and Dobson, C.M. (2003). Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 81:678–699.PubMedCrossRefGoogle Scholar
  105. Sunde, M., and Blake, C.C. (1997). F, the structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 50:123–159.PubMedGoogle Scholar
  106. Tan, S.Y., and Pepys, M.B. (1994). Amyloidosis. Histophathology 25:403–414.CrossRefGoogle Scholar
  107. Thomas, P.J., Qu, B.H., and Pedersen, P.L. (1995). Defective protein folding as a basis of human disease. Trends Bio Chem. Sci. 20:456–459.CrossRefGoogle Scholar
  108. Trieber, D.K., and Williamson, J.R. (1999). Exploring the kinetic traps in RNA folding, Curr. Opin. Struct. Biol. 9:339–345.CrossRefGoogle Scholar
  109. Uversky, V.N., and Fink, A.L. (2004). Conformational constraints for amyloid fibrillation: the importance of being unfolded. Biochim. Biophys. Acta 1698:131–153.PubMedGoogle Scholar
  110. Vendruscolo, M., and Dobson, C.M. (2005). Towards complete descriptions of the free energy landscapes of proteins. Philos. Trans. R. Soc. Lond A. 363:433–452.CrossRefGoogle Scholar
  111. Vendruscolo, M., Paci, E., Dobson, C.M., and Karplus, M. (2001). Three key residues form a critical contact network in a transition state for protein folding. Nature 409:641–646.PubMedCrossRefGoogle Scholar
  112. Vendruscolo, M., Zurdo, J., MacPhee, C.E., and Dobson, C.M. (2003). Protein folding and misfolding: a paradigm of self-assembly and regulation in complex biological systems. Philos. Trans. R. Soc. Lond. A 361:1205–1222.CrossRefGoogle Scholar
  113. Walsh, D.M., Klyubin, I., Fadeeva, J.V., Cullen, W.K., Anwyl, R., Wolfe, M.S., Rowan, M.J., and Selkoe, D.J. (2002). Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535–539.PubMedCrossRefGoogle Scholar
  114. Wille, H., Michelitsch, M.D., Guenebaut, V., Supattapone, S., Serban, A., Cohen, F.E., Agard, D.A., and Prusiner, S.B. (1999). Structural studies of the scrapie prion protein by electron crystallography. Proc. Natl. Acad. Sci. USA 99:3563–3568.CrossRefGoogle Scholar
  115. Wilson, M.R., and Easterbrook-Smith, S.B. (2000). Clusterin is a secreted mammalian chaperone. Trends Biochem. Sci. 25:95–98.PubMedCrossRefGoogle Scholar
  116. Wolfe, M.S. (2002). Secretase as a target for Alzheimer’s disease. Curr. Top. Med. Chem. 2:371–383.PubMedCrossRefGoogle Scholar
  117. Wolynes, P.G., Onuchic, J.N., and Thirumalai, D. (1995). Navigating the folding routes. Science 267:1619–1623.PubMedCrossRefGoogle Scholar
  118. Woolhead, C.A., McCormick, P.J., and Johnson, A.E. (2004). Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins. Cell 116:725–736.PubMedCrossRefGoogle Scholar
  119. Yusupov, M.M., Yusupova, G.Z., Baucom, A., Lieberman, K., Earnest, T.N., Cate, J.H., and Noller, H.F. (2001). Crystal structure of the ribosome at 5.5 Å resolution. Science 292:883–896.PubMedCrossRefGoogle Scholar
  120. Zurdo, J., Guijarro, J.I., Jiménez, J.L., Saibil, H.R., and Dobson, C.M. (2001). Dependence on solution conditions of aggregation and amyloid formation by an SH3 domain. J. Mol. Biol. 311:325–340.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Christopher M. Dobson
    • 1
  1. 1.Department of ChemistryUniversity of CambridgeCambridgeUK

Personalised recommendations

Cite chapter

Buy options