Kinetically competing huntingtin aggregation pathways control amyloid polymorphism and properties

Biochemistry

Volumn 51, Issue 13, 2012, Pages 2706-2716

  Jayaraman, Murali ^a,b   Mishra, Rakesh ^a   Kodali, Ravindra ^a   Thakur, Ashwani K ^a,c   Koharudin, Leonardus M I ^a   Gronenborn, Angela M ^a   Wetzel, Ronald ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b PFIZER INC   (United States)

^c INDIAN INSTITUTE OF TECHNOLOGY KANPUR   (India)

Author keywords

[No Author keywords available]

Indexed keywords

AGGREGATION INHIBITORS; AGGREGATION PROCESS; AMYLOID FORMATION; ASSEMBLY MECHANISM; HUNTINGTIN; N-TERMINALS; NUCLEATION MECHANISM; PEPTIDE-BASED INHIBITORS; POLYGLUTAMINE (POLYQ);

AGGLOMERATION; AMINO ACIDS; DISEASE CONTROL; KINETICS; NUCLEATION; OLIGOMERS;

GLYCOPROTEINS;

AMYLOID; HUNTINGTIN; OLIGOMER; POLYGLUTAMINE;

ALPHA HELIX; ARTICLE; CONTROLLED STUDY; MUTAGENESIS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN ASSEMBLY; PROTEIN DEGRADATION; PROTEIN POLYMORPHISM;

AMINO ACID SEQUENCE; HUMANS; KINETICS; MICROSCOPY, ELECTRON; MOLECULAR SEQUENCE DATA; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; POLYMORPHISM, GENETIC; SEQUENCE HOMOLOGY, AMINO ACID;

EID: 84859400325     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi3000929     Document Type: Article

References (68)

1. Bates, G. P. and Benn, C. (2002) The polyglutamine diseases, in Huntingtons Disease (Bates, G. P., Harper, P. S., and Jones, L., Eds.) pp 429-472, Oxford University Press, Oxford, UK.
2. Wetzel, R. (2012) Physical chemistry of polyglutamine: Intriguing tales of a monotonous sequence J. Mol. Biol. 10.1016/j.jmb.2012.01.030
3. Scherzinger, E., Sittler, A., Schweiger, K., Heiser, V., Lurz, R., Hasenbank, R., Bates, G. P., Lehrach, H., and Wanker, E. E. (1999) Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntingtons disease pathology Proc. Natl. Acad. Sci. U. S. A. 96, 4604-4609
4. Chen, S., Berthelier, V., Yang, W., and Wetzel, R. (2001) Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicity J. Mol. Biol. 311, 173-182
5. Wilburn, B., Rudnicki, D. D., Zhao, J., Weitz, T. M., Cheng, Y., Gu, X. F., Greiner, E., Park, C. S., Wang, N., Sopher, B. L., La Spada, A. R., Osmand, A., Margolis, R. L., Sun, Y. E., and Yang, X. W. (2011) An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntingtons disease-like 2 mice Neuron 70, 427-440
6. Wood, S. J., Maleeff, B., Hart, T., and Wetzel, R. (1996) Physical, morphological and functional differences between pH 5.8 and 7.4 aggregates of the Alzheimers peptide Ab J. Mol. Biol. 256, 870-877
7. Helms, L. R. and Wetzel, R. (1996) Specificity of abnormal assembly in immunoglobulin light chain deposition disease and amyloidosis J. Mol. Biol. 257, 77-86
8. Kirkitadze, M. D., Bitan, G., and Teplow, D. B. (2002) Paradigm shifts in Alzheimers disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies J. Neurosci. Res. 69, 567-577
9. Caughey, B. and Lansbury, P. T. (2003) Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders Annu. Rev. Neurosci. 26, 267-298
10. Glabe, C. G. and Kayed, R. (2006) Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis Neurology 66, S74-78
11. Kodali, R. and Wetzel, R. (2007) Polymorphism in the intermediates and products of amyloid assembly Curr. Opin. Struct. Biol. 17, 48-57
12. Ross, C. A. and Poirier, M. A. (2005) Opinion: What is the role of protein aggregation in neurodegeneration? Nat. Rev. Mol. Cell Biol. 6, 891-898
13. Sathasivam, K., Lane, A., Legleiter, J., Warley, A., Woodman, B., Finkbeiner, S., Paganetti, P., Muchowski, P. J., Wilson, S., and Bates, G. P. (2010) Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntingtons disease Hum. Mol. Genet. 19, 65-78
14. Chen, S., Ferrone, F., and Wetzel, R. (2002) Huntingtons Disease age-of-onset linked to polyglutamine aggregation nucleation Proc. Natl. Acad. Sci. U. S. A. 99, 11884-11889
15. Kar, K., Jayaraman, M., Sahoo, B., Kodali, R., and Wetzel, R. (2011) Critical nucleus size for disease-related polyglutamine aggregation is repeat-length dependent Nat. Struct. Mol. Biol. 18, 328-336
16. Thakur, A. K., Jayaraman, M., Mishra, R., Thakur, M., Chellgren, V. M., Byeon, I. J., Anjum, D. H., Kodali, R., Creamer, T. P., Conway, J. F., Gronenborn, A. M., and Wetzel, R. (2009) Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism Nat. Struct. Mol. Biol. 16, 380-389
17. Jayaraman, M., Kodali, R., Sahoo, B., Thakur, A. K., Mayasundari, A., Mishra, R., Peterson, C. B., and Wetzel, R. (2012) Slow amyloid nucleation via α-helix-rich oligomeric intermediates in short polyglutamine-containing Huntingtin fragments J. Mol. Biol. 415, 881-899
18. Mishra, R., Jayaraman, M., Roland, B. P., Landrum, E., Fullam, R., Kodali, R., Thakur, A. K., Arduini, I., and Wetzel, R. (2012) Inhibiting nucleation of amyloid structure in a huntingtin fragment by targeting α-helix rich oligomeric intermediates J. Mol. Biol. 415, 900-917
19. Nekooki-Machida, Y., Kurosawa, M., Nukina, N., Ito, K., Oda, T., and Tanaka, M. (2009) Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity Proc. Natl. Acad. Sci. U. S. A. 106, 9679-9684
20. Gupta, S., Jie, S., and Colby, D. W. (2011) Protein misfolding detected early in the pathogenesis of a transgenic mouse model of Huntingtons disease using an amyloid seeding assay J. Biol. Chem 10.1074/jbc.M111.305417
21. Nucifora, F. C., Jr., Sasaki, M., Peters, M. F., Huang, H., Cooper, J. K., Yamada, M., Takahashi, H., Tsuji, S., Troncoso, J., Dawson, V. L., Dawson, T. M., and Ross, C. A. (2001) Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity Science 291, 2423-2428
22. McCampbell, A. and Fischbeck, K. H. (2001) Polyglutamine and CBP: fatal attraction? Nat. Med. 7, 528-530
23. Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C. M., and Stefani, M. (2002) Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases Nature 416, 507-511
24. Poirier, M. A., Jiang, H., and Ross, C. A. (2005) A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structure Hum. Mol. Genet. 14, 765-774
25. Zhang, Q. C., Yeh, T. L., Leyva, A., Frank, L. G., Miller, J., Kim, Y. E., Langen, R., Finkbeiner, S., Amzel, M. L., Ross, C. A., and Poirier, M. A. (2011) A compact beta model of huntingtin toxicity J. Biol. Chem. 286, 8188-8196
26. ONuallain, B., Thakur, A. K., Williams, A. D., Bhattacharyya, A. M., Chen, S., Thiagarajan, G., and Wetzel, R. (2006) Kinetics and thermodynamics of amyloid assembly using a high-performance liquid chromatography-based sedimentation assay Methods Enzymol. 413, 34-74
27. Chen, S., Berthelier, V., Hamilton, J. B., ONuallain, B., and Wetzel, R. (2002) Amyloid-like features of polyglutamine aggregates and their assembly kinetics Biochemistry 41, 7391-7399
28. Jayaraman, M., Thakur, A. K., Kar, K., Kodali, R., and Wetzel, R. (2011) Assays for studying nucleated aggregation of polyglutamine proteins Methods 53, 246-254
29. Zuccato, C., Valenza, M., and Cattaneo, E. (2010) Molecular mechanisms and potential therapeutical targets in Huntingtons disease Physiol. Rev. 90, 905-981
30. Davies, S. W., Turmaine, M., Cozens, B. A., DiFiglia, M., Sharp, A. H., Ross, C. A., Scherzinger, E., Wanker, E. E., Mangiarini, L., and Bates, G. P. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation Cell 90, 537-548
31. Faber, P. W., Alter, J. R., MacDonald, M. E., and Hart, A. C. (1999) Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron Proc. Natl. Acad. Sci. U. S. A. 96, 179-184
32. Krobitsch, S. and Lindquist, S. (2000) Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins Proc. Natl. Acad. Sci. U. S. A. 97, 1589-1594
33. Apostol, B. L., Kazantsev, A., Raffioni, S., Illes, K., Pallos, J., Bodai, L., Slepko, N., Bear, J. E., Gertler, F. B., Hersch, S., Housman, D. E., Marsh, J. L., and Thompson, L. M. (2003) A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila Proc. Natl. Acad. Sci. U. S. A. 100, 5950-5955
34. Aiken, C. T., Tobin, A. J., and Schweitzer, E. S. (2004) A cell-based screen for drugs to treat Huntingtons disease Neurobiol. Dis. 16, 546-555
35. Wang, C. E., Tydlacka, S., Orr, A. L., Yang, S. H., Graham, R. K., Hayden, M. R., Li, S., Chan, A. W., and Li, X. J. (2008) Accumulation of N-terminal mutant huntingtin in mouse and monkey models implicated as a pathogenic mechanism in Huntingtons disease Hum. Mol. Genet. 17, 2738-2751
36. Sivanandam, V. N., Jayaraman, M., Hoop, C. L., Kodali, R., Wetzel, R., and van der Wel, P. C. (2011) The aggregation-enhancing huntingtin N-terminus is helical in amyloid fibrils J. Am. Chem. Soc. 133, 4558-4566
37. ONuallain, B., Williams, A. D., Westermark, P., and Wetzel, R. (2004) Seeding specificity in amyloid growth induced by heterologous fibrils J. Biol. Chem. 279, 17490-17499
38. Krebs, M. R., Morozova-Roche, L. A., Daniel, K., Robinson, C. V., and Dobson, C. M. (2004) Observation of sequence specificity in the seeding of protein amyloid fibrils Protein Sci. 13, 1933-1938
39. Colby, D. W., Garg, P., Holden, T., Chao, G., Webster, J. M., Messer, A., Ingram, V. M., and Wittrup, K. D. (2004) Development of a human light chain variable domain (V(L)) intracellular antibody specific for the amino terminus of huntingtin via yeast surface display J. Mol. Biol. 342, 901-912
40. Schiefner, A., Chatwell, L., Korner, J., Neumaier, I., Colby, D. W., Volkmer, R., Wittrup, K. D., and Skerra, A. (2011) A disulfide-free single-domain V(L) intrabody with blocking activity towards huntingtin reveals a novel mode of epitope recognition. J. Mol. Biol. 414, 337-355
41. Gray, M., Shirasaki, D. I., Cepeda, C., Andre, V. M., Wilburn, B., Lu, X.-H., Tao, J., Yamazaki, I., Li, S. -H., Sun, Y. -E., Li, X. -J., Levine, M. S., and Yang, X. W. (2008) Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice J. Neurosci. 28, 6182-6195
42. Stefani, M. (2010) Structural polymorphism of amyloid oligomers and fibrils underlies different fibrillization pathways: immunogenicity and cytotoxicity Curr. Protein Pept. Sci. 11, 343-354
43. Toyama, B. H. and Weissman, J. S. (2011) Amyloid structure: conformational diversity and consequences. Annu. Rev. Biochem. 80, 557-585
44. Glabe, C. G. (2008) Structural classification of toxic amyloid oligomers J. Biol. Chem. 283, 29639-29643
45. Goldsbury, C. S., Wirtz, S., Muller, S. A., Sunderji, S., Wicki, P., Aebi, U., and Frey, P. (2000) Studies on the in vitro assembly of a beta 1-40: implications for the search for a beta fibril formation inhibitors J. Struct. Biol. 130, 217-231
46. Paravastua, A. K., Leapman, R. D., Yau, W. M., and Tycko, R. (2008) Molecular structural basis for polymorphism in Alzheimers beta-amyloid fibrils Proc. Natl. Acad. Sci. U. S. A. 105, 18349-18354
47. Kodali, R., Williams, A. D., Chemuru, S., and Wetzel, R. (2010) A beta(1-40) forms five distinct amyloid structures whose beta-sheet contents and fibril stabilities are correlated. J. Mol. Biol. 401, 503-517
48. Wetzel, R., Shivaprasad, S., and Williams, A. D. (2007) Plasticity of amyloid fibrils Biochemistry 46, 1-10
49. Tanaka, M., Chien, P., Naber, N., Cooke, R., and Weissman, J. S. (2004) Conformational variations in an infectious protein determine prion strain differences Nature 428, 323-328
50. Kumar, S. and Udgaonkar, J. B. (2009) Conformational conversion may precede or follow aggregate elongation on alternative pathways of amyloid protofibril formation J. Mol. Biol. 385, 1266-1276
51. Kumar, S. and Udgaonkar, J. B. (2009) Structurally distinct amyloid protofibrils form on separate pathways of aggregation of a small protein Biochemistry 48, 6441-6449
52. Gu, X., Greiner, E. R., Mishra, R., Kodali, R., Osmand, A., Finkbeiner, S., Steffan, J. S., Thompson, L. M., Wetzel, R., and Yang, X. W. (2009) Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice Neuron 64, 828-840
53. Furukawa, Y., Kaneko, K., Yamanaka, K., and Nukina, N. (2010) Mutation-dependent polymorphism of Cu,Zn-superoxide dismutase aggregates in the familial form of amyotrophic lateral sclerosis J. Biol. Chem. 285, 22221-22231
54. Ding, F., Furukawa, Y., Nukina, N., and Dokholyan, N. V. Local Unfolding of Cu, Zn Superoxide Dismutase Monomer Determines the Morphology of Fibrillar Aggregates. J. Mol. Biol. 2011, not supplied.
55. Goldsbury, C., Frey, P., Olivieri, V., Aebi, U., and Muller, S. A. (2005) Multiple assembly pathways underlie amyloid-beta fibril polymorphisms J. Mol. Biol. 352, 282-298
56. Thakur, A. and Wetzel, R. (2002) Mutational analysis of the structural organization of polyglutamine aggregates Proc. Natl. Acad. Sci. U. S. A. 99, 17014-17019
57. Tam, S., Spiess, C., Auyeung, W., Joachimiak, L., Chen, B., Poirier, M. A., and Frydman, J. (2009) The chaperonin TRiC blocks a huntingtin sequence element that promotes the conformational switch to aggregation Nat. Struct. Mol. Biol. 16, 1279-1285
58. Williamson, T. E., Vitalis, A., Crick, S. L., and Pappu, R. V. (2010) Modulation of polyglutamine conformations and dimer formation by the N-terminus of huntingtin J. Mol. Biol. 396, 1295-1309
59. Fiumara, F., Fioriti, L., Kandel, E. R., and Hendrickson, W. A. (2010) Essential role of coiled coils for aggregation and activity of Q/N-rich prions and PolyQ proteins Cell 143, 1121-1135
60. 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
61. Tam, S., Geller, R., Spiess, C., and Frydman, J. (2006) The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions Nat. Cell Biol. 8, 1155-1162
62. Bhattacharyya, A., Thakur, A. K., Chellgren, V. M., Thiagarajan, G., Williams, A. D., Chellgren, B. W., Creamer, T. P., and Wetzel, R. (2006) Oligoproline effects on polyglutamine conformation and aggregation J. Mol. Biol. 355, 524-535
63. Steffan, J. S., Agrawal, N., Pallos, J., Rockabrand, E., Trotman, L. C., Slepko, N., Illes, K., Lukacsovich, T., Zhu, Y. Z., Cattaneo, E., Pandolfi, P. P., Thompson, L. M., and Marsh, J. L. (2004) SUMO modification of Huntingtin and Huntingtons disease pathology Science 304, 100-104
64. Atwal, R. S., Xia, J., Pinchev, D., Taylor, J., Epand, R. M., and Truant, R. (2007) Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity Hum. Mol. Genet. 16, 2600-2615
65. Rockabrand, E., Slepko, N., Pantalone, A., Nukala, V. N., Kazantsev, A., Marsh, J. L., Sullivan, P. G., Steffan, J. S., Sensi, S. L., and Thompson, L. M. (2007) The first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis Hum. Mol. Genet. 16, 61-77
66. Thompson, L. M., Aiken, C. T., Kaltenbach, L. S., Agrawal, N., Illes, K., Khoshnan, A., Martinez-Vincente, M., Arrasate, M., JG, O. S.-R., Khashwji, H., Lukacsovich, T., Zhu, Y. Z., Lau, A. L., Massey, A., Hayden, M. R., Zeitlin, S. O., Finkbeiner, S., Green, K. N., Laferla, F. M., Bates, G., Huang, L., Patterson, P. H., Lo, D. C., Cuervo, A. M., Marsh, J. L., and Steffan, J. S. (2009) IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome J. Cell Biol. 187, 1083-1099
67. Atwal, R. S., Desmond, C. R., Caron, N., Maiuri, T., Xia, J. R., Sipione, S., and Truant, R. (2011) Kinase inhibitors modulate huntingtin cell localization and toxicity Nat. Chem. Biol. 7, 453-460
68. Colby, D. W., Chu, Y., Cassady, J. P., Duennwald, M., Zazulak, H., Webster, J. M., Messer, A., Lindquist, S., Ingram, V. M., and Wittrup, K. D. (2004) Potent inhibition of huntingtin aggregation and cytotoxicity by a disulfide bond-free single-domain intracellular antibody Proc. Natl. Acad. Sci. U. S. A. 101, 17616-17621