Structural Disorder and Its Connection with Misfolding Diseases

  • Veronika Csizmók
  • Peter Tompa
Part of the Focus on Structural Biology book series (FOSB, volume 7)


Intrinsically disordered proteins or regions of proteins lack a well-defined structure, yet they carry out important functions often associated with the regulation of cell cycle and transcription. Due to these central roles in key cellular processes, their mutations are frequently involved in neurodegenerative diseases. These diseases are usually caused by the structural transition of disordered proteins to insoluble, highly ordered deposits termed amyloids, such a fate has been described in the case of Aβ peptide and tau protein in Alzheimer’s disease, α-synuclein in Parkinson’s disease or the polyglutamin stretch of huntingtin in Huntington’s disease and the prion protein in prion diseases. Due to the involvement of critical conformational change, these diseases are often denoted as “protein misfolding” diseases. Here we provide a brief overview of the rapidly expanding field of protein disorder to provide a conceptual background for the discussion of the essence of molecular mechanisms of these diseases. We will provide a brief overview of the field in general, directing focus on the tendency of disordered proteins for aggregation in vitro and also in vivo. We will provide some details on neurodegenerative diseases and the proteins involved. It will be shown that the underlying phenomenon of “misfolding” may also result in altering the normal function of proteins (physiological prions). We will wrap up the story by showing that the conformational transition occurs via partially ordered intermediates, which lead to a highly structured cross-β state in amyloids.


Prion Protein Prion Disease Structural Disorder Amyloid Formation Intrinsic Disorder 
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.


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  1. 1.
    Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6:197–208PubMedCrossRefGoogle Scholar
  2. 2.
    Tompa P (2002) Intrinsically unstructured proteins. Trends Biochem Sci 27:527–533PubMedCrossRefGoogle Scholar
  3. 3.
    Tompa P (2005) The interplay between structure and function in intrinsically unstructured proteins. FEBS Lett 579:3346–3354PubMedCrossRefGoogle Scholar
  4. 4.
    Uversky VN, Oldfield CJ, Dunker AK (2005) Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling. J Mol Recognit 18:343–384PubMedCrossRefGoogle Scholar
  5. 5.
    Wright PE, Dyson HJ (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol 293:321–331PubMedCrossRefGoogle Scholar
  6. 6.
    Uversky VN, Gillespie JR, Fink AL (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41:415–427PubMedCrossRefGoogle Scholar
  7. 7.
    Uversky VN (2002) Natively unfolded proteins: A point where biology waits for physics. Protein Sci 11:739–756PubMedCrossRefGoogle Scholar
  8. 8.
    Iakoucheva L, Brown C, Lawson J, Obradovic Z, Dunker A (2002) Intrinsic disorder in cell-signaling and cancer-associated. Proteins J Mol Biol 323:573–584CrossRefGoogle Scholar
  9. 9.
    Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT (2004) Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J Mol Biol 337:635–645PubMedCrossRefGoogle Scholar
  10. 10.
    Tompa P, Dosztányi Z, Simon I (2006) Prevalent structural disorder in E coli and S cerevisiae proteomes. J Proteome Res 5:1996–2000PubMedCrossRefGoogle Scholar
  11. 11.
    Dunker AK, Brown CJ, Lawson JD, Iakoucheva LM, Obradovic Z (2002) Intrinsic disorder and protein function. Biochemistry 41:6573–6582PubMedCrossRefGoogle Scholar
  12. 12.
    Tompa P, Szász C, Buday L (2005) Structural disorder throws new light on moonlighting. Trends Biochem Sci 30:484–489PubMedCrossRefGoogle Scholar
  13. 13.
    Iakoucheva LM, Radivojac P, Brown CJ, O’Connor TR, Sikes JG, Obradovic Z, Dunker AK (2004) The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res 32:1037–1049PubMedCrossRefGoogle Scholar
  14. 14.
    Schweers O, Schonbrunn-Hanebeck E, Marx A, Mandelkow E (1994) Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. J Biol Chem 269:24290–24297PubMedGoogle Scholar
  15. 15.
    Bell S, Klein C, Muller L, Hansen S, Buchner J (2002) p53 contains large unstructured regions in its native state. J Mol Biol 322:917–927PubMedCrossRefGoogle Scholar
  16. 16.
    Weinreb PH, Zhen W, Poon AW, Conway KA, Lansbury PT Jr (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35:13709–13715PubMedCrossRefGoogle Scholar
  17. 17.
    Lopez Garcia F, Zahn R, Riek R, Wuthrich K (2000) NMR structure of the bovine prion protein. Proc Natl Acad Sci USA 97:8334–8339PubMedCrossRefGoogle Scholar
  18. 18.
    Mark WY, Liao JC, Lu Y, Ayed A, Laister R, Szymczyna B, Chakrabartty A, Arrowsmith CH (2005) Characterization of segments from the central region of BRCA1: an intrinsically disordered scaffold for multiple protein-protein and protein-DNA interactions? J Mol Biol 345:275–287PubMedCrossRefGoogle Scholar
  19. 19.
    Sickmeier M, Hamilton JA, LeGall T, Vacic V, Cortese MS, Tantos A, Szabo B, Tompa P, Chen J, Uversky VN et al. (2007) DisProt: the database of disordered proteins. Nucleic Acids Res 35:D786–D793PubMedCrossRefGoogle Scholar
  20. 20.
    Ferron F, Longhi S, Canard B, Karlin D (2006) A practical overview of protein disorder prediction methods. Proteins 65:1–14PubMedCrossRefGoogle Scholar
  21. 21.
    Dosztányi Z, Sándor M, Tompa P, Simon I (2007) Prediction of protein disorder at the domain level. Curr Protein Pept Sci 8:161–171PubMedCrossRefGoogle Scholar
  22. 22.
    Dyson HJ, Wright PE (2004) Unfolded proteins and protein folding studied by NMR. Chem Rev 104:3607–3622PubMedCrossRefGoogle Scholar
  23. 23.
    Cortese MS, Baird JP, Uversky VN, Dunker AK (2005) Uncovering the unfoldome: enriching cell extracts for unstructured proteins by acid treatment. J Proteome Res 4:1610–1618PubMedCrossRefGoogle Scholar
  24. 24.
    Galea CA, Pagala VR, Obenauer JC, Park CG, Slaughter CA, Kriwacki RW (2006) Proteomic studies of the intrinsically unstructured mammalian proteome. J Proteome Res 5:2839–2848PubMedCrossRefGoogle Scholar
  25. 25.
    Tsvetkov P, Asher G, Paz A, Reuven N, Sussman JL, Silman I, Shaul Y (2008) Operational definition of intrinsically unstructured protein sequences based on susceptibility to the 20S proteasome. Proteins 70:1357–1366PubMedCrossRefGoogle Scholar
  26. 26.
    Csizmók V, Bokor M, Bánki P, Klement E, Medzihradszky KF, Friedrich P, Tompa K, Tompa P (2005) Primary contact sites in intrinsically unstructured proteins: the case of calpastatin and microtubule-associated protein 2. Biochemistry 44:3955–3964PubMedCrossRefGoogle Scholar
  27. 27.
    Szollosi E, Bokor M, Bodor A, Perczel A, Klement E, Medzihradszky KF, Tompa K, Tompa P (2008) Intrinsic structural disorder of DF31, a Drosophila protein of chromatin decondensation and remodeling activities. J Proteome Res 7:2291–2299PubMedCrossRefGoogle Scholar
  28. 28.
    von Ossowski I, Eaton JT, Czjzek M, Perkins SJ, Frandsen TP, Schulein M, Panine P, Henrissat B, Receveur-Brechot V (2005) Protein disorder: conformational distribution of the flexible linker in a chimeric double cellulase. Biophys J 88:2823–2832CrossRefGoogle Scholar
  29. 29.
    Zhu F, Kapitan J, Tranter GE, Pudney PD, Isaacs NW, Hecht L, Barron LD (2007) Residual structure in disordered peptides and unfolded proteins from multivariate analysis and ab initio simulation of Raman optical activity data. Proteins 70:823–833CrossRefGoogle Scholar
  30. 30.
    Watts JD, Cary PD, Sautiere P, Crane-Robinson C (1990) Thymosins: both nuclear and cytoplasmic proteins. Eur J Biochem 192:643–651PubMedCrossRefGoogle Scholar
  31. 31.
    Dobson CM (1993) Flexible friends Current Biology 3:530–532Google Scholar
  32. 32.
    Kriwacki RW, Hengst L, Tennant L, Reed SI, Wright PE (1996) Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity. Proc Natl Acad Sci USA 93:11504–11509PubMedCrossRefGoogle Scholar
  33. 33.
    Daughdrill GW, Hanely LJ, Dahlquist FW (1998) The C-terminal half of the anti-sigma factor FlgM contains a dynamic equilibrium solution structure favoring helical conformations. Biochemistry 37:1076–1082PubMedCrossRefGoogle Scholar
  34. 34.
    Sivakolundu SG, Bashford D, Kriwacki RW (2005) Disordered p27Kip1 exhibits intrinsic structure resembling the Cdk2/cyclin A-bound conformation. J Mol Biol 353:1118–1128PubMedCrossRefGoogle Scholar
  35. 35.
    Libich DS, Harauz G (2008) Backbone dynamics of the 18.5 kDa isoform of myelin basic protein reveals transient alpha-helices and a calmodulin-binding site. Biophys J 94:4847–4866PubMedCrossRefGoogle Scholar
  36. 36.
    Sugase K, Dyson HJ, Wright PE (2007) Mechanism of coupled folding and binding of an intrinsically disordered protein. Nature 447:1021–1025PubMedCrossRefGoogle Scholar
  37. 37.
    McNulty BC, Young GB, Pielak GJ (2006) Macromolecular crowding in the Escherichia coli periplasm maintains alpha-synuclein disorder. J Mol Biol 355:893–897PubMedCrossRefGoogle Scholar
  38. 38.
    Dunker AK, Lawson JD, Brown CJ, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J et al. (2001) Intrinsically disordered protein. J Mol Graphics Modelling 19:26–59CrossRefGoogle Scholar
  39. 39.
    Prilusky J, Felder CE, Zeev-Ben-Mordehai T, Rydberg EH, Man O, Beckmann JS, Silman I, Sussman JL (2005) FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded. Bioinformatics 21:3435–3438PubMedCrossRefGoogle Scholar
  40. 40.
    Garner E, Cannon P, Romero P, Obradovic Z, Dunker AK (1998) Predicting disordered regions from amino acid sequence: Common Themes despite differing structural characterization. Genome Inform Ser Workshop Genome Inform 9:201–213PubMedGoogle Scholar
  41. 41.
    Peng K, Radivojac P, Vucetic S, Dunker AK, Obradovic Z (2006) Length-dependent prediction of protein intrinsic disorder. BMC Bioinformatics 7:208PubMedCrossRefGoogle Scholar
  42. 42.
    Bordoli L, Kiefer F, Schwede1 T (2007) Assessment of disorder predictions in CASP7. Proteins 69 (Suppl 8):129–136Google Scholar
  43. 43.
    Dosztányi Z, Csizmók V, Tompa P, Simon I (2005) IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21:3433–3434PubMedCrossRefGoogle Scholar
  44. 44.
    Dosztányi Z, Csizmók V, Tompa P, Simon I (2005) The pairwise energy content estimated from amino acid composition discriminates between folded and instrinsically unstructured proteins. J Mol Biol 347:827–839PubMedCrossRefGoogle Scholar
  45. 45.
    Galzitskaya OV, Garbuzynskiy SO, Lobanov MY (2006) Fold Unfold: web server for the prediction of disordered regions in protein chain. Bioinformatics 22:2948–2949PubMedCrossRefGoogle Scholar
  46. 46.
    Schlessinger A, Punta M, Rost B (2007) Natively unstructured regions in proteins identified from contact predictions. Bioinformatics 23:2376–2384PubMedCrossRefGoogle Scholar
  47. 47.
    Ellis RJ (2001) Macromolecular crowding: obvious but under appreciated. Trends Biochem Sci 26:597–604PubMedCrossRefGoogle Scholar
  48. 48.
    Minton AP (2005) Models for excluded volume interaction between an unfolded protein and rigid macromolecular cosolutes: macromolecular crowding and protein stability revisited. Biophys J 88:971–985PubMedCrossRefGoogle Scholar
  49. 49.
    Baskakov I, Bolen DW (1998) Forcing thermodynamically unfolded proteins to fold. J Biol Chem 273:4831–4834PubMedCrossRefGoogle Scholar
  50. 50.
    Qu Y, Bolen DW (2002) Efficacy of macromolecular crowding in forcing proteins to fold. Biophys Chem 101–102:155–165PubMedCrossRefGoogle Scholar
  51. 51.
    Flaugh SL, Lumb KJ (2001) Effects of macromolecular crowding on the intrinsically disordered proteins c-Fos and p27(Kip1). Biomacromolecules 2:538–540PubMedCrossRefGoogle Scholar
  52. 52.
    Morar AS, Olteanu A, Young GB, Pielak GJ (2001) Solvent-induced collapse of alpha-synuclein and acid-denatured cytochrome c. Protein Sci 10:2195–2199PubMedCrossRefGoogle Scholar
  53. 53.
    Dedmon MM, Patel CN, Young GB, Pielak GJ (2002) FlgM gains structure in living cells. Proc Natl Acad Sci USA 99:12681–12684PubMedCrossRefGoogle Scholar
  54. 54.
    Bodart JF, Wieruszeski JM, Amniai L, Leroy A, Landrieu I, Rousseau-Lescuyer A, Vilain JP, Lippens G (2008) NMR observation of Tau in Xenopus oocytes. J Magn Reson 192:252–257PubMedCrossRefGoogle Scholar
  55. 55.
    Ellis RJ, Minton AP (2006) Protein aggregation in crowded environments. Biol Chem 387:485–497PubMedCrossRefGoogle Scholar
  56. 56.
    Uversky VN, E MC, Bower KS, Li J, Fink AL (2002) Accelerated alpha-synuclein fibrillation in crowded milieu. FEBS Lett 515:99–103PubMedCrossRefGoogle Scholar
  57. 57.
    Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366PubMedCrossRefGoogle Scholar
  58. 58.
    Fernandez A, Kardos J, Scott LR, Goto Y, Berry RS (2003) Structural defects and the diagnosis of amyloidogenic propensity. Proc Natl Acad Sci USA 100:6446–6451PubMedCrossRefGoogle Scholar
  59. 59.
    Chiti F, Stefani M, Taddei N, Ramponi G, Dobson CM (2003) Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature 424:805–808PubMedCrossRefGoogle Scholar
  60. 60.
    Fernandez-Escamilla AM, Rousseau F, Schymkowitz J, Serrano L (2004) Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins. Nat Biotechnol 22:1302–1306PubMedCrossRefGoogle Scholar
  61. 61.
    Linding R, Schymkowitz J, Rousseau F, Diella F, Serrano L (2004) A comparative study of the relationship between protein structure and beta-aggregation in globular and intrinsically disordered proteins. J Mol Biol 342:345–353PubMedCrossRefGoogle Scholar
  62. 62.
    Williams RM, Obradovic Z, Mathura V, Braun W, Garner EC, Young J, Takayama S, Brown CJ, Dunker AK (2001) The protein non-folding problem: amino acid determinants of intrinsic order and disorder. Pac Symp Biocomput 6:89–100Google Scholar
  63. 63.
    Monsellier E, Chiti F (2007) Prevention of amyloid-like aggregation as a driving force of protein evolution. EMBO Rep 8:737–742PubMedCrossRefGoogle Scholar
  64. 64.
    Parrini C, Taddei N, Ramazzotti M, Degl’Innocenti D, Ramponi G, Dobson CM, Chiti F (2005) Glycine residues appear to be evolutionarily conserved for their ability to inhibit aggregation. Structure 13:1143–1151PubMedCrossRefGoogle Scholar
  65. 65.
    Rousseau F, Serrano L, Schymkowitz JW (2006) How evolutionary pressure against protein aggregation shaped chaperone specificity. J Mol Biol 355:1037–1047PubMedCrossRefGoogle Scholar
  66. 66.
    Kirkitadze MD, Condron MM, Teplow DB (2001) Identification and characterization of key kinetic intermediates in amyloid beta-protein fibrillogenesis. J Mol Biol 312:1103–1119PubMedCrossRefGoogle Scholar
  67. 67.
    Dedmon MM, Lindorff-Larsen K, Christodoulou J, Vendruscolo M, Dobson CM (2005) Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations. J Am Chem Soc 127:476–477PubMedCrossRefGoogle Scholar
  68. 68.
    Vitalis A, Wang X, Pappu RV (2007) Quantitative characterization of intrinsic disorder in polyglutamine: insights from analysis based on polymer theories. Biophys J 93:1923–1937PubMedCrossRefGoogle Scholar
  69. 69.
    Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95:13363–13383PubMedCrossRefGoogle Scholar
  70. 70.
    Stahl N, Baldwin MA, Teplow DB, Hood L, Gibson BW, Burlingame AL, Prusiner SB (1993) Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry 32:1991–2002PubMedCrossRefGoogle Scholar
  71. 71.
    Donne DG, Viles JH, Groth D, Mehlhorn I, James TL, Cohen FE, Prusiner SB, Wright PE, Dyson HJ (1997) Structure of the recombinant full-length hamster prion protein PrP(29-231): the N terminus is highly flexible Proc Natl Acad Sci USA 94:13452–13457PubMedCrossRefGoogle Scholar
  72. 72.
    Chien P, Weissman JS, DePace AH (2004) Emerging principles of conformation-based prion inheritance. Annu Rev Biochem 73:617–656PubMedCrossRefGoogle Scholar
  73. 73.
    Fowler DM, Koulov AV, Balch WE, Kelly JW (2007) Functional amyloid–from bacteria to humans. Trends Biochem Sci 32:217–224PubMedCrossRefGoogle Scholar
  74. 74.
    Wickner RB, Taylor KL, Edskes HK, Maddelein ML (2000) Prions: Portable prion domains. Curr Biol 10:R335–R337PubMedCrossRefGoogle Scholar
  75. 75.
    Lindquist S (1997) Mad cows meet psi-chotic yeast: the expansion of the prion hypothesis. Cell 89:495–498PubMedCrossRefGoogle Scholar
  76. 76.
    Nelson R, Sawaya MR, Balbirnie M, Madsen AO, Riekel C, Grothe R, Eisenberg D (2005) Structure of the cross-beta spine of amyloid-like fibrils. Nature 435:773–778PubMedCrossRefGoogle Scholar
  77. 77.
    Li L, Lindquist S (2000) Creating a protein-based element of inheritance. Science 287:661–664PubMedCrossRefGoogle Scholar
  78. 78.
    Si K, Giustetto M, Etkin A, Hsu R, Janisiewicz AM, Miniaci MC, Kim JH, Zhu H, Kandel ER (2003) A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia. Cell 115:893–904PubMedCrossRefGoogle Scholar
  79. 79.
    Si K, Lindquist S, Kandel ER (2003) A neuronal isoform of the aplysia CPEB has prion-like properties. Cell 115:879–891PubMedCrossRefGoogle Scholar
  80. 80.
    Come JH, Fraser PE, Lansbury PT Jr (1993) A kinetic model for amyloid formation in the prion diseases: importance of seeding. Proc Natl Acad Sci USA 90:5959–5963PubMedCrossRefGoogle Scholar
  81. 81.
    Jarrett JT, Lansbury PT Jr (1993) Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie? Cell 73:1055–1058PubMedCrossRefGoogle Scholar
  82. 82.
    Uversky VN, Fink AL (2004) Conformational constraints for amyloid fibrillation: the importance of being unfolded. Biochim Biophys Acta 1698:131–153PubMedGoogle Scholar
  83. 83.
    Booth DR, Sunde M, Bellotti V, Robinson CV, Hutchinson WL, Fraser PE, Hawkins PN, Dobson CM, Radford SE, Blake CC at al. (1997) Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 385:787–793Google Scholar
  84. 84.
    Lashuel HA, Wurth C, Woo L, Kelly JW (1999) The most pathogenic transthyretin variant, L55P, forms amyloid fibrils under acidic conditions and protofilaments under physiological conditions. Biochemistry 38:13560–13573PubMedCrossRefGoogle Scholar
  85. 85.
    Wall J, Schell M, Murphy C, Hrncic R, Stevens FJ, Solomon A (1999) Thermodynamic instability of human lambda 6 light chains: correlation with fibrillogenicity. Biochemistry 38:14101–14108PubMedCrossRefGoogle Scholar
  86. 86.
    Guijarro JI, Sunde M, Jones JA, Campbell ID, Dobson CM (1998) Amyloid fibril formation by an SH3 domain. Proc Natl Acad Sci USA 95:4224–4228PubMedCrossRefGoogle Scholar
  87. 87.
    Litvinovich SV, Brew SA, Aota S, Akiyama SK, Haudenschild C, Ingham KC (1998) Formation of amyloid-like fibrils by self-association of a partially unfolded fibronectin type III module. J Mol Biol 280:245–258PubMedCrossRefGoogle Scholar
  88. 88.
    Dobson CM (1999) Protein misfolding, evolution and disease. Trends Biochem Sci 24:329–332PubMedCrossRefGoogle Scholar
  89. 89.
    Chiti F, Taddei N, Stefani M, Dobson CM, Ramponi G (2001) Reduction of the amyloidogenicity of a protein by specific binding of ligands to the native conformation. Protein Sci 10:879–886PubMedCrossRefGoogle Scholar
  90. 90.
    Uversky VN, Li J, Fink AL (2001) Evidence for a partially folded intermediate in alpha-synuclein fibril formation. J Biol Chem 276:10737–10744PubMedCrossRefGoogle Scholar
  91. 91.
    Kayed R, Bernhagen J, Greenfield N, Sweimeh K, Brunner H, Voelter W, Kapurniotu A (1999) Conformational transitions of islet amyloid polypeptide (IAPP) in amyloid formation in vitro. J Mol Biol 287:781–796PubMedCrossRefGoogle Scholar
  92. 92.
    Sunde M, Blake C (1997) The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv Protein Chem 50:123–159PubMedCrossRefGoogle Scholar
  93. 93.
    Rousseau F, Schymkowitz J, Serrano L (2006) Protein aggregation and amyloidosis: confusion of the kinds? Curr Opin Struct Biol 16:118–126PubMedCrossRefGoogle Scholar
  94. 94.
    Perutz MF, Staden R, Moens L, De Baere I (1993) Polar zippers. Curr Biol 3:249–253PubMedCrossRefGoogle Scholar
  95. 95.
    Ferguson N, Berriman J, Petrovich M, Sharpe TD, Finch JT, Fersht AR (2003) Rapid amyloid fiber formation from the fast-folding WW domain FBP28. Proc Natl Acad Sci USA 100:9814–9819PubMedCrossRefGoogle Scholar
  96. 96.
    Petkova AT, Ishii Y, Balbach JJ, Antzutkin ON, Leapman RD, Delaglio F, Tycko R (2002) A structural model for Alzheimer’s beta -amyloid fibrils based on experimental constraints from solid state NMR. Proc Natl Acad Sci USA 99:16742–16747PubMedCrossRefGoogle Scholar
  97. 97.
    Torok M, Milton S, Kayed R, Wu P, McIntire T, Glabe CG, Langen R (2002) Structural and dynamic features of Alzheimer’s Abeta peptide in amyloid fibrils studied by site-directed spin labeling. J Biol Chem 277:40810–40815PubMedCrossRefGoogle Scholar
  98. 98.
    Chen M, Margittai M, Chen J, Langen R (2007) Investigation of alpha-synuclein fibril structure by site-directed spin labeling. J Biol Chem 282:24970–24979PubMedCrossRefGoogle Scholar
  99. 99.
    Cobb NJ, Sonnichsen FD, McHaourab H, Surewicz WK (2007) Molecular architecture of human prion protein amyloid: a parallel, in-register beta-structure. Proc Natl Acad Sci USA 104:18946–18951PubMedCrossRefGoogle Scholar
  100. 100.
    Hoshino M, Katou H, Hagihara Y, Hasegawa K, Naiki H, Goto Y (2002) Mapping the core of the beta(2)-microglobulin amyloid fibril by H/D exchange. Nat Struct Biol 9:332–336PubMedCrossRefGoogle Scholar
  101. 101.
    Kajava AV, Aebi U, Steven AC (2005) The parallel superpleated beta-structure as a model for amyloid fibrils of human amylin. J Mol Biol 348:247–252PubMedCrossRefGoogle Scholar
  102. 102.
    Krishnan R, Lindquist SL (2005) Structural insights into a yeast prion illuminate nucleation and strain diversity. Nature 435:765–772PubMedCrossRefGoogle Scholar
  103. 103.
    Govaerts C, Wille H, Prusiner SB, Cohen FE (2004) Evidence for assembly of prions with left-handed beta-helices into trimers. Proc Natl Acad Sci USA 101:8342–8347PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Veronika Csizmók
    • 1
  • Peter Tompa
  1. 1.Institute of Enzymology Biological Research Center Hungarian Academy of SciencesBudapestHungary

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