Interactions between Hsp70 and the hydrophobic core of α-synuclein inhibit fibril assembly

Biochemistry

Volumn 47, Issue 47, 2008, Pages 12614-12625

  Luk, Kelvin C ^a   Mills, Ian P ^a   Trojanowski, John Q ^a   Lee, Virginia M Y ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGGLOMERATION; FLOW INTERACTIONS; HYDROPHOBICITY; MICROSCOPIC EXAMINATION; MODULATION;

ASSEMBLY PROCESSES; BINDING ASSAYS; COFACTORS; CRITICAL STEPS; DELETION MUTANTS; ELECTRON MICROSCOPY.; FIBRIL ASSEMBLIES; FLUORESCENCE POLARIZATIONS; HEAT SHOCK PROTEIN 70; HYDROPHOBIC CORES; HYDROPHOBIC REGIONS; IN VITRO ASSEMBLIES; INSOLUBLE FIBRILS; KEY COMPONENTS; MOLECULAR CHAPERONES; NEURODEGENERATIVE DISEASES; PARKINSON'S DISEASES; PROTEIN MISFOLDING; SUBSTOICHIOMETRIC CONCENTRATIONS; SUBSTRATE BINDINGS; SYNUCLEIN;

PROTEINS;

ALPHA SYNUCLEIN; AMYLOID; CHAPERONE; HEAT SHOCK PROTEIN 70;

ARTICLE; BINDING ASSAY; CONTROLLED STUDY; DELETION MUTANT; ELECTRON MICROSCOPY; ENZYME SUBSTRATE COMPLEX; FLUORESCENCE POLARIZATION; HUMAN; HUMAN CELL; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN ASSEMBLY; PROTEIN INTERACTION;

ALPHA-SYNUCLEIN; BRAIN; FLUORESCENCE POLARIZATION; HSP70 HEAT-SHOCK PROTEINS; HUMANS; HYDROPHOBICITY; KINETICS; MICROSCOPY, ELECTRON; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN ISOFORMS; SEQUENCE DELETION; SOLUBILITY; TIME FACTORS;

EID: 56749117866     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi801475r     Document Type: Article

References (56)

1. Forman, M. S., Lee, V. M. Y., and Trojanowski, J. Q. (2005) Nosology of Parkinson's disease: Looking for the way out of a quackmire. Neuron 47, 479-482.
2. Spillantini, M. G., Schmidt, M. L., Lee, V. M. Y., Trojanowski, J. Q., Jakes, R., and Goedert, M. (1997) α-Synuclein in Lewy bodies. Nature 388, 839-840.
3. Spillantini, M. G. (1999) Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are α-synucleinopathies. Parkinsonism Relat. Disorders 5, 157-162.
4. Wakabayashi, K., Hayashi, S., Kakita, A., Yamada, M., Toyoshima, Y., Yoshimoto, M., and Takahashi, H. (1998) Accumulation of α-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol. 96, 445-452.
5. Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., Lincoln, S., Crawley, A., Hanson, M., Maraganore, D., Adler, C., Cookson, M. R., Muenter, M., Baptista, M., Miller, D., Blancato, J., Hardy, J., and Gwinn-Hardy, K. (2003) α-Synuclein locus triplication causes Parkinson's disease. Science 302, 841.
6. Zarranz, J. J., Alegre, J., Gomez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atares, B., Llorens, V., Tortosa, E. G., del Ser, T., Munoz, D. G., and de Yebenes, J. G. (2004) The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55, 164-173.
7. Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E. S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W. G., Lazzarini, A. M., Duvoisin, R. C., Dilorio, G., Golbe, L. I., and Nussbaum, R. L. (1997) Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047.
8. Auluck, P. K., Chan, H. Y. E., Trojanowski, J. Q., Lee, V. M. Y., and Bonini, N. M. (2002) Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295, 865-868.
9. Masliah, E., Rockenstein, E., Veinbergs, I., Mallory, M., Hashimoto, M., Takeda, A., Sagara, Y., Sisk, A., and Mucke, L. (2000) Dopaminergic loss and inclusion body formation in α-synuclein mice: Implications for neurodegenerative disorders. Science 287, 1265-1269.
10. Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., and Lee, V. M. Y. (2002) Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein. Neuron 34, 521-533.
11. Hartl, F. U., and Hayer-Hartl, M. (2002) Protein folding-Molecular chaperones in the cytosol: From nascent chain to folded protein. Science 295, 1852-1858.
12. Magrane, J., Smith, R. C., Walsh, K., and Querfurth, H. W. (2004) Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed β-amyloid in neurons. J. Neurosci. 24, 1700-1706.
13. 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. U.S.A. 97, 7841-7846.
14. Warrick, J. M., Chan, H. Y. E., Gray-Board Chai, Y. H., Paulson, H. L., and Bonini, N. M. (1999) Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat. Genet. 23, 425-428.
15. Klucken, J., Shin, Y., Masliah, E., Hyman, B. T., and Mclean, P. J. (2004) Hsp70 reduces α-synuclein aggregation and toxicity. J. Biol. Chem. 279, 25497-25502.
16. Uryu, K., Richter-Landsberg, C., Welch, W., Sun, E., Goldbaum, O., Norris, E. H., Pham, C. T., Yazawa, I., Hilburger, K., Micsenyi, M., Giasson, B. I., Bonini, N. M., Lee, V. M. Y., and Trojanowski, J. Q. (2006) Convergence of heat shock protein 90 with ubiquitin in filamentous α-synuclein inclusions of α-synucleinopathies. Am. J. Pathol. 168, 947-961.
17. Mclean, P. J., Kawamata, H., Shariff, S., Hewett, J., Sharma, N., Ueda, K., Breakefield, X. O., and Hyman, B. T. (2002) TorsinA and heat shock proteins act as molecular chaperones: Suppression of α-synuclein aggregation. J. Neurochem. 83, 846-854.
18. Yaglom, J. A., Gabai, V. L., Meriin, A. B., Mosser, D. D., and Sherman, M. Y. (1999) The function of HSP72 in suppression of c-Jun N-terminal kinase activation can be dissociated from its role in prevention of protein damage. J. Biol. Chem. 274, 20223-20228.
19. Huang, C. J., Cheng, H., Hao, S. F., Zhou, H., Zhang, X. J., Gao, J. N., Sun, Q. H., Hu, H. Y., and Wang, C. C. (2006) Heat shock protein 70 inhibits α-synuclein fibril formation via interactions with diverse intermediates. J. Mol. Biol. 364, 323-336.
20. Dedmon, M. M., Christodoulou, J., Wilson, M. R., and Dobson, C. M. (2005) Heat shock protein 70 inhibits α-synuclein fibril formation via preferential binding to prefibrillar species. J. Biol. Chem. 280, 14733-14740.
21. Wu, B., Hunt, C., and Morimoto, R. (1985) Structure and Expression of the Human-Gene Encoding Major Heat-Shock Protein Hsp70. Mol. Cell. Biol. 5, 330-341.
22. Brown, I. R. (2007) Heat shock proteins and protection of the nervous system. Stress Responses Biol. Med. 1113, 147-158.
23. Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., Cooke, M. P., Walker, J. R., and Hogenesch, J. B. (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl. Acad. Sci. U.S.A. 101, 6062-6067.
24. Giasson, B. I., Uryu, K., Trojanowski, J. Q., and Lee, V. M. Y. (1999) Mutant and wild type human α-synucleins assemble into elongated filaments with distinct morphologies in vitro. J. Biol. Chem. 274, 7619-7622.
25. Freeman, B. C., Myers, M. P., Schumacher, R., and Morimoto, R. I. (1995) Identification of a Regulatory Motif in Hsp70 That Affects Atpase Activity, Substrate-Binding and Interaction with Hdj-1. EMBO J. 14, 2281-2292.
26. Crystal, A. S., Giasson, B. I., Crowe, A., Kung, M. P., Zhuang, Z. P., Trojanowski, J. Q., and Lee, V. M. Y. (2003) A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114. J. Neurochem. 86, 1359-1368.
27. Giasson, B. I., Jakes, R., Goedert, M., Duda, J. E., Leight, S., Trojanowski, J. Q., and Lee, V. M. Y. (2000) A panel of epitope-specific antibodies detects protein domains distributed throughout human α-synuclein in Lewy bodies of Parkinson's disease. J. Neurosci. Res. 59, 528-533.
28. Jakes, R., Crowther, R. A., Lee, V. M. Y., Trojanowski, J. Q., Iwatsubo, T., and Goedert, M. (1999) Epitope mapping of LB509, a monoclonal antibody directed against human α-synuclein. Neurosci. Lett. 269, 13-16.
29. Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q., and Lee, V. M. Y. (2001) A hydrophobic stretch of 12 amino acid residues in the middle of α-synuclein is essential for filament assembly. J. Biol. Chem. 276, 2380-2386.
30. Luk, K. C., Hyde, E. G., Trojanowski, J. Q., and Lee, V. M. Y. (2007) Sensitive fluorescence polarization technique for rapid screening of α-synuclein oligomerization/fibrillization inhibitors. Biochemistry 46, 12522-12529.
31. Hashimoto, M., Hsu, L. J., Sisk, A., Xia, Y., Takeda, A., Sundsmo, M., and Masliah, E. (1998) Human recombinant NACP/α-synuclein is aggregated and fibrillated in vitro: Relevance for Lewy body disease. Brain Res. 799, 301-306.
32. Zhu, M., Rajamani, S., Kaylor, J., Han, S., Zhou, F. M., and Fink, A. L. (2004) The flavonoid baicalein inhibits fibrillation of α-synuclein and disaggregates existing fibrils. J. Biol. Chem. 279, 26846-26857.
33. Murray, I. V. J., Giasson, B. I., Quinn, S. M., Koppaka, V., Axelsen, P. H., Ischiropoulos, H., Trojanowski, J. Q., and Lee, V. M. Y. (2003) Role of α-synuclein carboxy-terminus on fibril formation in vitro. Biochemistry 42, 8530-8540.
34. Lockhart, A., Ye, L., Judd, D. B., Merritt, A. T., Lowe, P. N., Morgenstern, J. L., Hong, G. Z., Gee, A. D., and Brown, J. (2005) Evidence for the presence of three distinct binding sites for the thioflavin T class of Alzheimer's disease PET imaging agents on β-amyloid peptide fibrils. J. Biol. Chem. 280, 7677-7684.
35. Bertoncini, C. W., Jung, Y. S., Fernandez, C. O., Hoyer, W., Griesinger, C., Jovin, T. M., and Zweckstetter, M. (2005) Release of long-range tertiary interactions potentiates aggregation of natively unstructured α-synuclein. Proc. Natl. Acad. Sci. U.S.A. 102, 1430-1435.
36. Serpell, L. C., Berriman, J., Jakes, R., Goedert, M., and Crowther, R. A. (2000) Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation. Proc. Natl. Acad. Sci. U.S.A. 97, 4897-4902.
37. Crowther, R. A., Jakes, R., Spillantini, M. G., and Goedert, M. (1998) Synthetic filaments assembled from C-terminally truncated α-synuclein. FEBS Lett. 436, 309-312.
38. Cuervo, A. M., Stefanie, L., Fredenburg, R., Lansbury, P. T., and Sulzer, D. (2004) Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science 305, 1292-1295.
39. Han, H. Y., Weinreb, P. H., and Lansbury, P. T. (1995) The Core Alzheimers Peptide Nac Forms Amyloid Fibrils Which Seed and Are Seeded by β-Amyloid: Is Nac a Common Trigger or Target in Neurodegenerative Disease. Chem. Biol. 2, 163-169.
40. Benaroudj, N., Batelier, G., Triniolles, F., and Ladjimi, M. M. (1995) Self-Association of the Molecular Chaperone Hsc70. Biochemistry 34, 15282-15290.
41. Benaroudj, N., Triniolles, F., and Ladjimi, M. M. (1996) Effect of nucleotides, peptides, and unfolded proteins on the self-association of the molecular chaperone HSC70. J. Biol. Chem. 271, 18471-18476.
42. Evans, C. G., Wisen, S., and Gestwicki, J. E. (2006) Heat shock proteins 70 and 90 inhibit early stages of amyloid β-(1-42) aggregation in vitro. J. Biol. Chem. 281, 33182-33191.
43. Wacker, J. L., Zareie, M. H., Fong, H., Sarikaya, M., and Muchowski, P. J. (2004) Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat. Struct. Mol. Biol. 11, 1215-1222.
44. Buchberger, A., Theyssen, H., Schroder, H., Mccarty, J. S., Virgallita, G., Milkereit, P., Reinstein, J., and Bukau, B. (1995) Nucleotide-Induced Conformational-Changes in the Atpase and Substrate-Binding Domains of the Dnak Chaperone Provide Evidence for Interdomain Communication. J. Biol. Chem. 270, 16903-16910.
45. Greene, L. E., Zinner, R., Naficy, S., and Eisenberg, E. (1995) Effect of Nucleotide on the Binding of Peptides to 70-Kda Heat-Shock Protein. J. Biol. Chem. 270, 2967-2973.
46. Rudiger, S., Germeroth, L., SchneiderMergener, J., and Bukau, B. (1997) Substrate specificity of the DnaK chaperone determined by screening cellulose-bound peptide libraries. EMBO J. 16, 1501-1507.
47. Fourie, A. M., Sambrook, J. F., and Gething, M. J. H. (1994) Common and Divergent Peptide Binding Specificities of Hsp70 Molecular Chaperones. J. Biol. Chem. 269, 30470-30478.
48. Kaylor, J., Bodner, N., Edridge, S., Yamin, G., Hong, D. P., and Fink, A. L. (2005) Characterization of oligomeric intermediates in α-synuclein fibrillation: FRET studies of Y125W/Y133F/Y136F α-synuclein. J. Mol. Biol. 353, 357-372.
49. Norris, E. H., Giasson, B. I., Hodara, R., Xu, S. H., Trojanowski, J. Q., Ischiropoulos, H., and Lee, V. M. Y. (2005) Reversible inhibition of α-synuclein fibrillization by dopaminochrome-mediated conformational alterations. J. Biol. Chem. 280, 21212-21219.
50. Rao, J. N., Dua, V., and Ulmer, T. S. (2008) Characterization of α-synuclein interactions with selected aggregation-inhibiting small molecules. Biochemistry 47, 4651-4656.
51. Ehrnhoefer, D. E., Bieschke, J., Boeddrich, A., Herbst, M., Masino, L., Lurz, R., Engemann, S., Pastore, A., and Wanker, E. E. (2008) EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat. Struct. Mol. Biol. 15, 558-566.
52. Masuda, M., Suzuki, N., Taniguchi, S., Oikawa, T., Nonaka, T., Iwatsubo, T., Hisanaga, S., Goedert, M., and Hasegawa, M. (2006) Small molecule inhibitors of α-synuclein filament assembly. Biochemistry 45, 6085-6094.
53. Li, J., Zhu, M., Rajamani, S., Uversky, V. N., and Fink, A. L. (2004) Rifampicin inhibits α-synuclein fibrillation and disaggregates fibrils. Chem. Biol. 11, 1513-1521.
54. Conway, K. A., Rochet, J. C., Bieganski, R. M., and Lansbury, P. T. (2001) Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct. Science 294, 1346-1349.
55. Yagi, H., Kusaka, E., Hongo, K., Mizobata, T., and Kawata, Y. (2005) Amyloid fibril formation of α-synuclein is accelerated by preformed amyloid seeds of other proteins: Implications for the mechanism of transmissible conformational diseases. J. Biol. Chem. 280, 38609-38616.
56. Wood, S. J., Wypych, J., Steavenson, S., Louis, J. C., Citron, M., and Biere, A. L. (1999) α-Synuclein fibrillogenesis is nucleation-dependent: Implications for the pathogenesis of Parkinson's disease. J. Biol. Chem. 274, 19509-19512.