Structural features and domain organization of huntingtin fibrils

Journal of Biological Chemistry

Volumn 287, Issue 38, 2012, Pages 31739-31746

  Bugg, Charles W ^a,b   Isas, J Mario ^b   Fischer, Torsten ^b   Patterson, Paul H ^a   Langen, Ralf ^b  

^a CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BUILDING STRUCTURAL; C-TERMINAL DOMAINS; ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY; HELICAL STRUCTURES; HUNTINGTIN; HUNTINGTON DISEASE; MISFOLDING; N-TERMINAL DOMAINS; POLYGLUTAMINE (POLYQ); POLYPROLINE II; SITE-DIRECTED SPIN LABELING; SPIN-SPIN INTERACTION; STRUCTURAL FEATURE;

AMINO ACIDS; MAGNETIC RESONANCE; MODEL STRUCTURES; MOLECULES; PARAMAGNETISM;

ELECTRON SPIN RESONANCE SPECTROSCOPY;

HUNTINGTIN; POLYGLUTAMINE;

AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; ELECTRON SPIN RESONANCE; EXON; FIBER; MOLECULAR INTERACTION; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DOMAIN; PROTEIN QUATERNARY STRUCTURE; PROTEIN STRUCTURE; PROTEIN TERTIARY STRUCTURE; SPIN LABELING;

BIOCHEMISTRY; CIRCULAR DICHROISM; ELECTRON SPIN RESONANCE SPECTROSCOPY; EXONS; HUMANS; MUTAGENESIS, SITE-DIRECTED; NERVE TISSUE PROTEINS; PEPTIDES; PROTEIN CONFORMATION; PROTEIN DENATURATION; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT PROTEINS; THIOREDOXINS;

EID: 84866419575     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.353839     Document Type: Article

References (59)

1. The Huntington Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington disease chromosomes. Cell 72, 971-983
2. Zoghbi, H. Y., and Orr, H. T. (2000) Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23, 217-247 (Pubitemid 30350043)
3. Brinkman, R. R., Mezei, M. M., Theilmann, J., Almqvist, E., and Hayden, M. R. (1997) The likelihood of being affected with Huntington disease by a particular age, for a specificCAGsize. Am. J. Hum. Genet. 60, 1202-1210 (Pubitemid 27194105)
4. Vonsattel, J. P., Myers, R. H., Stevens, T. J., Ferrante, R. J., Bird, E. D., and Richardson, E. P., Jr. (1985) Neuropathological classification of Huntington disease. J. Neuropathol. Exp. Neurol. 44, 559-577
5. Rosas, H. D., Goodman, J., Chen, Y. I., Jenkins, B. G., Kennedy, D. N., Makris, N., Patti, M., Seidman, L. J., Beal, M. F., and Koroshetz, W. J. (2001) Striatal volume loss in HD as measured by MRI and the influence of CAG repeat. Neurology 57, 1025-1028 (Pubitemid 32880197)
6. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S. W., and Bates, G. P. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493-506 (Pubitemid 26374323)
7. DiFiglia, M., Sapp, E., Chase, K. O., Davies, S. W., Bates, G. P., Vonsattel, J. P., and Aronin, N. (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990-1993 (Pubitemid 27449140)
8. Sieradzan, K. A., Mechan, A. O., Jones, L., Wanker, E. E., Nukina, N., and Mann, D. M. (1999) Huntington disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp. Neurol. 156, 92-99 (Pubitemid 29152986)
9. Huang, C. C., Faber, P. W., Persichetti, F., Mittal, V., Vonsattel, J. P., MacDonald, M. E., and Gusella, J. F. (1998) Amyloid formation by mutant huntingtin: threshold, progressivity and recruitment of normal polyglutamine proteins. Somat. Cell. Mol. Genet. 24, 217-233 (Pubitemid 29316230)
10. Poirier, M. A., Li, H., Macosko, J., Cai, S., Amzel, M., and Ross, C. A. (2002) Huntingtin spheroids and protofibrils as precursors in polyglutamine fibrilization. J. Biol. Chem. 277, 41032-41037 (Pubitemid 35215693)
11. Perutz, M. F., Pope, B. J., Owen, D., Wanker, E. E., and Scherzinger, E. (2002) Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid β-peptide of amyloid plaques. Proc. Natl. Acad. Sci. U.S.A. 99, 5596-5600 (Pubitemid 34411594)
12. Jahn, T. R., Makin, O. S., Morris, K. L., Marshall, K. E., Tian, P., Sikorski, P., and Serpell, L. C. (2010) The common architecture of cross-β amyloid. J. Mol. Biol. 395, 717-727
13. 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 (Pubitemid 32735322)
14. Chen, S., Berthelier, V., Hamilton, J. B., O'Nuallain, B., and Wetzel, R. (2002) Amyloid-like features of polyglutamine aggregates and their assembly kinetics. Biochemistry 41, 7391-7399 (Pubitemid 34602457)
15. 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
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 1Nterminus triggers a complex aggregation mechanism. Nat. Struct. Mol. Biol. 16, 380-389
17. 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
18. 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 subcellular localization, aggregation and effects on calcium homeostasis. Hum. Mol. Genet. 16, 61-77 (Pubitemid 46156597)
19. 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
20. Mishra, R., Jayaraman, M., Roland, B. P., Landrum, E., Fullam, T., Kodali, R., Thakur, A. K., Arduini, I., and Wetzel, R. (2012) Inhibiting the nucleation of amyloid structure in a huntingtin fragment by targeting α-helix-rich oligomeric intermediates. J. Mol. Biol. 415, 900-917
21. 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
22. Hollenbach, B., Scherzinger, E., Schweiger, K., Lurz, R., Lehrach, H., and Wanker, E. E. (1999) Aggregation of truncated GST-HD exon 1 fusion proteins containing normal range and expanded glutamine repeats. Philos. Trans. R. Soc. Lond. B Biol. Sci. 354, 991-994 (Pubitemid 29477959)
23. Whitmore, L., and Wallace, B. A. (2008) Protein secondary structure analyses from circular dichroism spectroscopy: methods and reference databases. Biopolymers 89, 392-400
24. Compton, L. A., and Johnson, W. C., Jr. (1986) Analysis of protein circular dichroism spectra for secondary structure using a simple matrix multiplication. Anal. Biochem. 155, 155-167 (Pubitemid 16034476)
25. Manavalan, P., and Johnson, W. C., Jr. (1987) Variable selection method improves the prediction of protein secondary structure from circular dichroism spectra. Anal. Biochem. 167, 76-85
26. Sreerama, N., and Woody, R. W. (2000) Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set. Anal. Biochem. 287, 252-260 (Pubitemid 32006234)
27. Sreerama, N., and Woody, R. W. (1993) A self-consistent method for the analysis of protein secondary structure from circular dichroism. Anal. Biochem. 209, 32-44 (Pubitemid 23084702)
28. Andrade, M. A., Chacón, P., Merelo, J. J., and Morán, F. (1993) Evaluation of secondary structure of proteins from UV circular dichroism spectra using an unsupervised learning neural network. Protein Eng. 6, 383-390 (Pubitemid 23197398)
29. Sreerama, N., Venyaminov, S. Y., and Woody, R. W. (1999) Estimation of the number of α-helical and β-strand segments in proteins using circular dichroism spectroscopy. Protein Sci. 8, 370-380 (Pubitemid 29072437)
30. Provencher, S. W., and Glöckner, J. (1981) Estimation of globular protein secondary structure from circular dichroism. Biochemistry 20, 33-37
31. van Stokkum, I. H., Spoelder, H. J., Bloemendal, M., van Grondelle, R., and Groen, F. C. (1990) Estimation of protein secondary structure and error analysis from circular dichroism spectra. Anal. Biochem. 191, 110-118
32. Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, B., Hasenbank, R., Bates, G. P., Davies, S. W., Lehrach, H., and Wanker, E. E. (1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90, 549-558 (Pubitemid 27347244)
33. 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 Huntington disease pathology. Proc. Natl. Acad. Sci. U.S.A. 96, 4604-4609 (Pubitemid 29190383)
34. Bennett, M. J., Huey-Tubman, K. E., Herr, A. B., West, A. P., Jr., Ross, S. A., and Bjorkman, P. J. (2002) Inaugural Article: a linear lattice model for polyglutamine in CAG-expansion diseases. Proc. Natl. Acad. Sci. U.S.A. 99, 11634-11639 (Pubitemid 34994451)
35. Langen, R., Cai, K., Altenbach, C., Khorana, H. G., and Hubbell, W. L. (1999) Structural features of the C-terminal domain of bovine rhodopsin: a site-directed spin-labeling study. Biochemistry 38, 7918-7924
36. Margittai, M., Fasshauer, D., Jahn, R., and Langen, R. (2003) The Habc domain and the SNARE core complex are connected by a highly flexible linker. Biochemistry 42, 4009-4014 (Pubitemid 36418293)
37. 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
38. Margittai, M., and Langen, R. (2008) Fibrils with parallel in-register structure constitute a major class of amyloid fibrils: molecular insights from electron paramagnetic resonance spectroscopy. Q. Rev. Biophys. 41, 265-297
39. 2-microglobulin in amyloid fibrils revealed by site-directed spin labeling and chemical labeling. J. Biol. Chem. 285, 17137-17147
40. Chen, M., Margittai, M., Chen, J., and Langen, R. (2007) Investigation of α-synuclein fibril structure by site-directed spin labeling. J. Biol. Chem. 282, 24970-24979 (Pubitemid 47347515)
41. Margittai, M., and Langen, R. (2004) Template-assisted filament growth by parallel stacking of tau. Proc. Natl. Acad. Sci. U.S.A. 101, 10278-10283 (Pubitemid 38924916)
42. Hubbell, W. L., Cafiso, D. S., and Altenbach, C. (2000) Identifying conformational changes with site-directed spin labeling. Nat. Struct. Biol. 7, 735-739
43. Lakhani, V. V., Ding, F., and Dokholyan, N. V. (2010). Polyglutamine-induced misfolding of huntingtin exon1 is modulated by the flanking sequences. PLoS Comput. Biol. 6, e1000772
44. Darnell, G., Orgel, J. P., Pahl, R., and Meredith, S. C. (2007) Flanking polyproline sequences inhibit β-sheet structure in polyglutamine segments by inducing PPII-like helix structure. J. Mol. Biol. 374, 688-704 (Pubitemid 350027728)
45. Kelly, M. A., Chellgren, B. W., Rucker, A. L., Troutman, J. M., Fried, M. G., Miller, A. F., and Creamer, T. P. (2001) Host-guest study of left-handed polyproline II helix formation. Biochemistry 40, 14376-14383 (Pubitemid 33111719)
46. Horng, J. C., and Raines, R. T. (2006) Stereoelectronic effects on polyproline conformation. Protein Sci. 15, 74-83
47. Woody, R. W. (1992) Circular dichroism of unordered peptides. Adv. Biophys. Chem. 2, 37-79
48. Mchaourab, H. S., Lietzow, M. A., Hideg, K., and Hubbell, W. L. (1996) Motion of spin-labeled side chains in T4 lysozyme: correlation with protein structure and dynamics. Biochemistry 35, 7692-7704 (Pubitemid 26202511)
49. Török, M., Milton, S., Kayed, R., Wu, P., McIntire, T., Glabe, C. G., and Langen, R. (2002) Structural and dynamic features of Alzheimer's Aβ peptide in amyloid fibrils studied by site-directed spin labeling. J. Biol. Chem. 277, 40810-40815 (Pubitemid 35215666)
50. 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
51. 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 (Pubitemid 41785754)
52. Kim, M. W., Chelliah, Y., Kim, S. W., Otwinowski, Z., and Bezprozvanny, I. (2009) Secondary structure of Huntingtin amino-terminal region. Structure 17, 1205-1212
53. Ko, J., Ou, S., and Patterson, P. H. (2001) New anti-huntingtin monoclonal antibodies: implications for huntingtin conformation and its binding proteins. Brain Res. Bull. 56, 319-329 (Pubitemid 33062356)
54. Legleiter, J., Lotz, G. P., Miller, J., Ko, J., Ng, C., Williams, G. L., Finkbeiner, S., Patterson, P. H., and Muchowski, P. J. (2009) Monoclonal antibodies recognize distinct conformational epitopes formed by polyglutamine in a mutant huntingtin fragment. J. Biol. Chem. 284, 21647-21658
55. Thakur, A. K., and Wetzel, R. (2002) Mutational analysis of the structural organization of polyglutamine aggregates. Proc. Natl. Acad. Sci. U.S.A. 99, 17014-17019 (Pubitemid 36034090)
56. Sharma, D., Shinchuk, L. M., Inouye, H., Wetzel, R., and Kirschner, D. A. (2005) Polyglutamine homopolymers having 8-45 residues form slablike β-crystallite assemblies. Proteins 61, 398-411 (Pubitemid 41429147)
57. 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 β-sheet structure. Hum. Mol. Genet. 14, 765-774 (Pubitemid 40403273)
58. Jao, C. C., Hegde, B. G., Chen, J., Haworth, I. S., and Langen, R. (2008) Structure of membrane-bound α-synuclein from site-directed spin labeling and computational refinement. Proc. Natl. Acad. Sci. U.S.A. 105, 19666-19671
59. Bedrood, S., Li, Y., Isas, J. M., Hegde, B. G., Baxa, U., Haworth, I. S., and Langen, R. (2012) Fibril structure of human islet amyloid polypeptide. J. Biol. Chem. 287, 5235-5241