Folding of the RNA Recognition Motif (RRM) domains of the Amyotrophic Lateral Sclerosis (ALS)-linked protein TDP-43 reveals an intermediate state

Journal of Biological Chemistry

Volumn 289, Issue 12, 2014, Pages 8264-8276

  Mackness, Brian C ^a   Tran, Meme T ^a   McClain, Shannan P ^a   Matthews, C Robert ^a   Zitzewitz, Jill A ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLUSTER ANALYSIS; FLUORESCENCE SPECTROSCOPY; PROTEINS; RNA;

AMYOTROPHIC LATERAL SCLEROSIS; CD AND FLUORESCENCE SPECTROSCOPY; CONFORMATIONAL CHANGE; CYTOPLASMIC INCLUSION; NUCLEAR EXPORT SIGNALS; RNA-RECOGNITION MOTIFS; STABILIZING INTERACTIONS; THREE-STATE EQUILIBRIUM;

NEURODEGENERATIVE DISEASES;

RNA BINDING PROTEIN; RNA RECOGNITION MOTIF 1; RNA RECOGNITION MOTIF 2; TAR DNA BINDING PROTEIN; UNCLASSIFIED DRUG;

AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; BINDING AFFINITY; CONFORMATIONAL TRANSITION; DNA BINDING; HUMAN; HUMAN TISSUE; HYDROPHOBICITY; NUCLEAR EXPORT SIGNAL; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CLEAVAGE; PROTEIN CONFORMATION; PROTEIN DENATURATION; PROTEIN DOMAIN; PROTEIN FOLDING; PROTEIN PROTEIN INTERACTION; PROTEIN RNA BINDING; PROTEIN STABILITY; PROTEIN UNFOLDING; SEQUENCE HOMOLOGY;

AMYOTROPHIC LATERAL SCLEROSIS (LOU GEHRIG'S DISEASE); CIRCULAR DICHROISM (CD); FLUORESCENCE; FRONTOTEMPORAL LOBAR DEGENERATION (FTLD); NEURODEGENERATIVE DISEASES; PROTEIN FOLDING; PROTEIN MISFOLDING; PROTEIN-NUCLEIC ACID INTERACTION; RNA-BINDING PROTEIN; THERMODYNAMICS;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; AMYOTROPHIC LATERAL SCLEROSIS; DNA-BINDING PROTEINS; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN STABILITY; PROTEIN STRUCTURE, TERTIARY; RNA; SEQUENCE ALIGNMENT; THERMODYNAMICS;

EID: 84896950092     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.542779     Document Type: Article

References (78)

1. Da Cruz, S., and Cleveland, D. W. (2011) Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr. Opin. Neurobiol. 21, 904-919
2. Turner, M. R., Hardiman, O., Benatar, M., Brooks, B. R., Chio, A., de Carvalho, M., Ince, P. G., Lin, C., Miller, R. G., Mitsumoto, H., Nicholson, G., Ravits, J., Shaw, P. J., Swash, M., Talbot, K., Traynor, B. J., Van den Berg, L. H., Veldink, J. H., Vucic, S., and Kiernan, M. C. (2013) Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol. 12, 310-322
3. Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., McCluskey, L. F., Miller, B. L., Masliah, E., Mackenzie, I. R., Feldman, H., Feiden, W., Kretzschmar, H. A., Trojanowski, J. Q., and Lee, V. M. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133 (Pubitemid 44547757)
4. Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., and Oda, T. (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 351, 602-611 (Pubitemid 44708852)
5. Chen-Plotkin, A. S., Lee, V. M., and Trojanowski, J. Q. (2010) TAR DNA-binding protein 43 in neurodegenerative disease. Nat. Rev. Neurol. 6, 211-220
6. Lee, E. B., Lee, V. M., and Trojanowski, J. Q. (2012) Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat. Rev. Neurosci. 13, 38-50
7. Buratti, E., and Baralle, F. E. (2008) Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front. Biosci. 13, 867-878 (Pubitemid 351594732)
8. Lagier-Tourenne, C., Polymenidou, M., and Cleveland, D. W. (2010) TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum. Mol. Genet. 19, R46-R64
9. Igaz, L. M., Kwong, L. K., Xu, Y., Truax, A. C., Uryu, K., Neumann, M., Clark, C. M., Elman, L. B., Miller, B. L., Grossman, M., McCluskey, L. F., Trojanowski, J. Q., and Lee, V. M. (2008) Enrichment of C-terminal fragments in TAR DNA-binding protein-43 cytoplasmic inclusions in brain but not in spinal cord of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Am. J. Pathol. 173, 182-194 (Pubitemid 351947966)
10. Ross, C. A., and Poirier, M. A. (2004) Protein aggregation and neurodegenerative disease. Nat. Med. 10, S10-S17 (Pubitemid 38901862)
11. Xu, Z.-S. (2012) Does a loss of TDP-43 function cause neurodegeneration? Mol. Neurodegener. 7, 27
12. Johnson, B. S., McCaffery, J. M., Lindquist, S., and Gitler, A. D. (2008) A yeast TDP-43 proteinopathy model: exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc. Natl. Acad. Sci. U.S.A. 105, 6439-6444 (Pubitemid 351758364)
13. Igaz, L. M., Kwong, L. K., Chen-Plotkin, A., Winton, M. J., Unger, T. L., Xu, Y., Neumann, M., Trojanowski, J. Q., and Lee, V. M. (2009) Expression of TDP-43 C-terminal fragments in vitro recapitulates pathological features of TDP-43 proteinopathies. J. Biol. Chem. 284, 8516-8524
14. Zhang, Y.-J., Xu, Y.-F., Cook, C., Gendron, T. F., Roettges, P., Link, C. D., Lin, W.-L., Tong, J., Castanedes-Casey, M., Ash, P., Gass, J., Rangachari, V., Buratti, E., Baralle, F., Golde, T. E., Dickson, D. W., and Petrucelli, L. (2009) Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc. Natl. Acad. Sci. U.S.A. 106, 7607-7612
15. Yang, C., Tan, W., Whittle, C., Qiu, L., Cao, L., Akbarian, S., and Xu, Z. (2010) The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PLoS One 5, e15878
16. Fernandez-Escamilla, A. M., Rousseau, F., Schymkowitz, J., and Serrano, L. (2004) Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins. Nat. Biotechnol. 22, 1302-1306 (Pubitemid 39336784)
17. Romero, P., Obradovic, Z., Li, X., Garner, E. C., Brown, C. J., and Dunker, A. K. (2001) Sequence complexity of disordered protein. Proteins 42, 38-48
18. Uversky, V. N., Oldfield, C. J., and Dunker, A. K. (2008) Intrinsically disordered proteins in human diseases: introducing the D2 concept. Annu. Rev. Biophys. 37, 215-246
19. Cléry, A., Blatter, M., and Allain, F. H. (2008) RNA recognition motifs. Boring? Not quite. Curr. Opin. Struct. Biol. 18, 290-298
20. Daubner, G. M., Cléry, A., and Allain, F. H. (2013) RRM-RNA recognition. NMR or crystallography . . . and new findings. Curr. Opin. Struct. Biol. 23, 100-108
21. Buratti, E., and Baralle, F. E. (2001) Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. J. Biol. Chem. 276, 36337-36343
22. Huang, Y.-C., Lin, K.-F., He, R.-Y., Tu, P.-H., Koubek, J., Hsu, Y.-C., and Huang, J. J. (2013) Inhibition of TDP-43 aggregation by nucleic acid binding. PLoS One 8, e64002
23. Ayala, Y. M., De Conti, L., Avendaño-Vázquez, S. E., Dhir, A., Romano, M., D'Ambrogio, A., Tollervey, J., Ule, J., Baralle, M., Buratti, E., and Baralle, F. E. (2011) TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J. 30, 277-288
24. Lucast, L. J., Batey, R. T., and Doudna, J. A. (2001) Large-scale purification of a stable form of recombinant tobacco etch virus protease. BioTechniques 30, 544-546, 548, 550 passim
25. Gill, S. C., and von Hippel, P. H. (1989) Calculation of protein extinction coefficients from amino acid sequence data. Anal. Biochem. 182, 319-326 (Pubitemid 19277112)
26. Greenfield, N. J. (2006) Using circular dichroism spectra to estimate protein secondary structure. Nat. Protoc. 1, 2876-2890
27. Bilsel, O., Zitzewitz, J. A., Bowers, K. E., and Matthews, C. R. (1999) Folding mechanism of the α-subunit of tryptophan synthase, an α/β barrel protein: global analysis highlights the interconversion of multiple native, intermediate, and unfolded forms through parallel channels. Biochemistry 38, 1018-1029
28. Pace, C. N. (1986) Determination and analysis of urea and guanidine hydrochloride denaturation curves. Methods Enzymol. 131, 266-280
29. Finn, B. E., Chen, X., Jennings, P., Saalau-Bethell, S. M., and Matthews, C. R. (1992) in Protein Engineering. A Practical Approach (Rees, A. R., Sternberg, M. J. E., and Wetzel, R., eds) pp. 167-189, Oxford University Press, London
30. Pagano, J. M., Farley, B. M., McCoig, L. M., and Ryder, S. P. (2007) Molecular basis of RNA recognition by the embryonic polarity determinant MEX-5. J. Biol. Chem. 282, 8883-8894 (Pubitemid 47093472)
31. Pagano, J. M., Clingman, C. C., and Ryder, S. P. (2011) Quantitative approaches to monitor protein-nucleic acid interactions using fluorescent probes. RNA 17, 14-20
32. Iko, Y., Kodama, T. S., Kasai, N., Oyama, T., Morita, E. H., Muto, T., Okumura, M., Fujii, R., Takumi, T., Tate, S., and Morikawa, K. (2004) Domain architectures and characterization of an RNA-binding protein, TLS. J. Biol. Chem. 279, 44834-44840 (Pubitemid 39430895)
33. Kurihara, Y., Nagata, T., Imai, T., Hiwatashi, A., Horiuchi, M., Sakakibara, S., Katahira, M., Okano, H., and Uesugi, S. (1997) Structural properties and RNA-binding activities of two RNA recognition motifs of a mouse neural RNA-binding protein, mouse-Musashi-1. Gene 186, 21-27 (Pubitemid 27084825)
34. Lu, J., and Hall, K. B. (1995) An RBD that does not bind RNA: NMR secondary structure determination and biochemical properties of the C-terminal RNA binding domain from the human U1A protein. J. Mol. Biol. 247, 739-752
35. Kabsch, W., and Sander, C. (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22, 2577-2637
36. Joosten, R. P., te Beek, T. A., Krieger, E., Hekkelman, M. L., Hooft, R. W., Schneider, R., Sander, C., and Vriend, G. (2011) A series of PDB related databases for everyday needs. Nucleic Acids Res. 39, D411-D419
37. Berova, N., Nakanishi, K., and Woody, R. W. (eds) (2000) Circular Dichroism. Principles and Applications, 2nd Ed., pp. 601-620, Wiley-VCH, Inc., New York
38. Wang, Y.-T., Kuo, P.-H., Chiang, C.-H., Liang, J.-R., Chen, Y.-R., Wang, S., Shen, J. C., and Yuan, H. S. (2013) The truncated C-terminal RNA recognition motif of TDP-43 protein plays a key role in forming proteinaceous aggregates. J. Biol. Chem. 288, 9049-9057
39. Shodai, A., Morimura, T., Ido, A., Uchida, T., Ayaki, T., Takahashi, R., Kitazawa, S., Suzuki, S., Shirouzu, M., Kigawa, T., Muto, Y., Yokoyama, S., Takahashi, R., Kitahara, R., Ito, H., Fujiwara, N., and Urushitani, M. (2013) Aberrant assembly of RNA recognition motif 1 links to pathogenic conversion of TAR DNA-binding protein of 43 kDa (TDP-43). J. Biol. Chem. 288, 14886-14905
40. Chang, C.-K., Chiang, M.-H., Toh, E. K.-W., Chang, C.-F., and Huang, T.-H. (2013) Molecular mechanism of oxidation-induced TDP-43 RRM1 aggregation and loss of function. FEBS Lett. 587, 575-582
41. Baldwin, R. L. (1986) Temperature dependence of the hydrophobic interaction in protein folding. Proc. Natl. Acad. Sci. U.S.A. 83, 8069-8072
42. Schellman, J. A. (1997) Temperature, stability, and the hydrophobic interaction. Biophys. J. 73, 2960-2964
43. Lukavsky, P. J., Daujotyte, D., Tollervey, J. R., Ule, J., Stuani, C., Buratti, E., Baralle, F. E., Damberger, F. F., and Allain, F. H. (2013) Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43. Nat. Struct. Mol. Biol. 20, 1443-1449
44. Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., and Deng, H. X. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62 (Pubitemid 23087289)
45. Kabashi, E., Valdmanis, P. N., Dion, P., Spiegelman, D., McConkey, B. J., Vande Velde, C., Bouchard, J.-P., Lacomblez, L., Pochigaeva, K., Salachas, F., Pradat, P.-F., Camu, W., Meininger, V., Dupre, N., and Rouleau, G. A. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574 (Pubitemid 351601218)
46. Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., Baralle, F., de Belleroche, J., Mitchell, J. D., Leigh, P. N., Al-Chalabi, A., Miller, C. C., Nicholson, G., and Shaw, C. E. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672 (Pubitemid 351432505)
47. Kwiatkowski, T. J., Jr., Bosco, D. A., Leclerc, A. L., Tamrazian, E., Vanderburg, C. R., Russ, C., Davis, A., Gilchrist, J., Kasarskis, E. J., Munsat, T., Valdmanis, P., Rouleau, G. A., Hosler, B. A., Cortelli, P., de Jong, P. J., Yoshinaga, Y., Haines, J. L., Pericak-Vance, M. A., Yan, J., Ticozzi, N., Siddique, T., McKenna-Yasek, D., Sapp, P. C., Horvitz, H. R., Landers, J. E., and Brown, R. H., Jr. (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205-1208
48. Wu, C.-H., Fallini, C., Ticozzi, N., Keagle, P. J., Sapp, P. C., Piotrowska, K., Lowe, P., Koppers, M., McKenna-Yasek, D., Baron, D. M., Kost, J. E., Gonzalez-Perez, P., Fox, A. D., Adams, J., Taroni, F., Tiloca, C., Leclerc, A. L., Chafe, S. C., Mangroo, D., Moore, M. J., Zitzewitz, J. A., Xu, Z.-S., van den Berg, L. H., Glass, J. D., Siciliano, G., Cirulli, E. T., Goldstein, D. B., Salachas, F., Meininger, V., Rossoll, W., Ratti, A., Gellera, C., Bosco, D. A., Bassell, G. J., Silani, V., Drory, V. E., Brown, R. H., Jr., and Landers, J. E. (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488, 499-503
49. DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., Kouri, N., Wojtas, A., Sengdy, P., Hsiung, G.-Y., Karydas, A., Seeley, W. W., Josephs, K. A., Coppola, G., Geschwind, D. H., Wszolek, Z. K., Feldman, H., Knopman, D. S., Petersen, R. C., Miller, B. L., Dickson, D. W., Boylan, K. B., Graff-Radford, N. R., and Rademakers, R. (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245-256
50. Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., Kalimo, H., Paetau, A., Abramzon, Y., Remes, A. M., Kaganovich, A., Scholz, S. W., Duckworth, J., Ding, J., Harmer, D. W., Hernandez, D. G., Johnson, J. O., Mok, K., Ryten, M., Trabzuni, D., Guerreiro, R. J., Orrell, R. W., Neal, J., Murray, A., Pearson, J., Jansen, I. E., Sondervan, D., Seelaar, H., Blake, D., Young, K., Halliwell, N., Callister, J. B., Toulson, G., Richardson, A., Gerhard, A., Snowden, J., Mann, D., Neary, D., Nalls, M. A., Peuralinna, T., Jansson, L., Isoviita, V.-M., Kaivorinne, A.-L., Hölttä-Vuori, M., Ikonen, E., Sulkava, R., Benatar, M., Wuu, J., Chiò, A., Restagno, G., Borghero, G., Sabatelli, M., ITALSGEN Consortium, Heckerman, D., Rogaeva, E., Zinman, L., Rothstein, J. D., Sendtner, M., Drepper, C., Eichler, E. E., Alkan, C., Abdullaev, Z., Pack, S. D., Dutra, A., Pak, E., Hardy, J., Singleton, A., Williams, N. M., Heutink, P., Pickering-Brown, S., Morris, H. R., Tienari, P. J., and Traynor, B. J. (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257-268
51. Chen, S., Sayana, P., Zhang, X., and Le, W. (2013) Genetics of amyotrophic lateral sclerosis: an update. Mol. Neurodegener. 8, 28
52. Youmans, K. L., and Wolozin, B. (2012) TDP-43. A new player on the AD field? Exp. Neurol. 237, 90-95
53. Rayaprolu, S., Fujioka, S., Traynor, S., Soto-Ortolaza, A. I., Petrucelli, L., Dickson, D. W., Rademakers, R., Boylan, K. B., Graff-Radford, N. R., Uitti, R. J., Wszolek, Z. K., and Ross, O. A. (2013) TARDBP mutations in Parkinson's disease. Parkinsonism Relat. Disord. 19, 312-315
54. Janssens, J., and Van Broeckhoven, C. (2013) Pathological mechanisms underlying TDP-43 driven neurodegeneration in FTLD-ALS spectrum disorders. Hum. Mol. Genet. 22, R77-R87
55. Geser, F., Lee, V. M., and Trojanowski, J. Q. (2010) Amyotrophic lateral sclerosis and frontotemporal lobar degeneration: a spectrum of TDP-43 proteinopathies. Neuropathology 30, 103-112
56. Saini, A., and Chauhan, V. S. (2011) Delineation of the core aggregation sequences of TDP-43 C-terminal fragment. Chembiochem 12, 2495-2501
57. Furukawa, Y., Kaneko, K., and Nukina, N. (2011) Molecular properties of TAR DNA binding protein-43 fragments are dependent upon its cleavage site. Biochim. Biophys. Acta 1812, 1577-1583
58. Budini, M., Romano, V., Avendaño-Vázquez, S. E., Bembich, S., Buratti, E., and Baralle, F. E. (2012) Role of selected mutations in the Q/N-rich region of TDP-43 in EGFP-12xQ/N-induced aggregate formation. Brain Res. 1462, 139-150
59. Dormann, D., Capell, A., Carlson, A. M., Shankaran, S. S., Rodde, R., Neumann, M., Kremmer, E., Matsuwaki, T., Yamanouchi, K., Nishihara, M., and Haass, C. (2009) Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin. J. Neurochem. 110, 1082-1094
60. Nonaka, T., Kametani, F., Arai, T., Akiyama, H., and Hasegawa, M. (2009) Truncation and pathogenic mutations facilitate the formation of intracellular aggregates of TDP-43. Hum. Mol. Genet. 18, 3353-3364
61. Zhang, Y.-J., Xu, Y.-F., Dickey, C. A., Buratti, E., Baralle, F., Bailey, R., Pickering-Brown, S., Dickson, D., and Petrucelli, L. (2007) Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J. Neurosci. 27, 10530-10534 (Pubitemid 47501990)
62. Takagi, S., Iguchi, Y., Katsuno, M., Ishigaki, S., Ikenaka, K., Fujioka, Y., Honda, D., Niwa, J., Tanaka, F., Watanabe, H., Adachi, H., and Sobue, G. (2013) RNP2 of RNA recognition motif 1 plays a central role in the aberrant modification of TDP-43. PLoS ONE 8, e66966
63. Chen, A. K., Lin, R. Y., Hsieh, E. Z., Tu, P.-H., Chen, R. P., Liao, T.-Y., Chen, W., Wang, C.-H., and Huang, J. J. (2010) Induction of amyloid fibrils by the C-terminal fragments of TDP-43 in amyotrophic lateral sclerosis. J. Am. Chem. Soc. 132, 1186-1187
64. Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S., Ayala, Y. M., and Baralle, F. E. (2005) TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J. Biol. Chem. 280, 37572-37584 (Pubitemid 41642366)
65. D'Ambrogio, A., Buratti, E., Stuani, C., Guarnaccia, C., Romano, M., Ayala, Y. M., and Baralle, F. E. (2009) Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo. Nucleic Acids Res. 37, 4116-4126
66. Kuo, P.-H., Doudeva, L. G., Wang, Y.-T., Shen, C.-K., and Yuan, H. S. (2009) Structural insights into TDP-43 in nucleic-acid binding and domain interactions. Nucleic Acids Res. 37, 1799-1808
67. Gu, Z., Zitzewitz, J. A., and Matthews, C. R. (2007) Mapping the structure of folding cores in TIM barrel proteins by hydrogen exchange mass spectrometry: the roles of motif and sequence for the indole-3-glycerol phosphate synthase from Sulfolobus solfataricus. J. Mol. Biol. 368, 582-594 (Pubitemid 46483489)
68. Gu, Z., Rao, M. K., Forsyth, W. R., Finke, J. M., and Matthews, C. R. (2007) Structural analysis of kinetic folding intermediates for a TIM barrel protein, indole-3-glycerol phosphate synthase, by hydrogen exchange mass spectrometry and Gō model simulation. J. Mol. Biol. 374, 528-546 (Pubitemid 350007646)
69. Wu, Y., Vadrevu, R., Kathuria, S., Yang, X., and Matthews, C. R. (2007) A tightly packed hydrophobic cluster directs the formation of an off-pathway sub-millisecond folding intermediate in the α subunit of tryptophan synthase, a TIM barrel protein. J. Mol. Biol. 366, 1624-1638 (Pubitemid 46215600)
70. Kathuria, S. V., Day, I. J., Wallace, L. A., and Matthews, C. R. (2008) Kinetic traps in the folding of beta alpha-repeat proteins: CheY initially misfolds before accessing the native conformation. J. Mol. Biol. 382, 467-484
71. Sobolev, V., Sorokine, A., Prilusky, J., Abola, E. E., and Edelman, M. (1999) Automated analysis of interatomic contacts in proteins. Bioinformatics 15, 327-332 (Pubitemid 29213759)
72. la Cour, T., Kiemer, L., Mølgaard, A., Gupta, R., Skriver, K., and Brunak, S. (2004) Analysis and prediction of leucine-rich nuclear export signals. Protein Eng. Des. Sel. 17, 527-536 (Pubitemid 39487532)
73. Winton, M. J., Igaz, L. M., Wong, M. M., Kwong, L. K., Trojanowski, J. Q., and Lee, V. M. (2008) Disturbance of nuclear and cytoplasmic TAR DNA-binding protein (TDP-43) induces disease-like redistribution, sequestration, and aggregate formation. J. Biol. Chem. 283, 13302-13309
74. Ito, D., Seki, M., Tsunoda, Y., Uchiyama, H., and Suzuki, N. (2011) Nuclear transport impairment of amyotrophic lateral sclerosis-linked mutations in FUS/TLS. Ann. Neurol. 69, 152-162
75. Liu, X., Niu, C., Ren, J., Zhang, J., Xie, X., Zhu, H., Feng, W., and Gong, W. (2013) The RRM domain of human fused in sarcoma protein reveals a non-canonical nucleic acid binding site. Biochim. Biophys. Acta 1832, 375-385
76. Kawahara, Y., and Mieda-Sato, A. (2012) TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc. Natl. Acad. Sci. U.S.A. 109, 3347-3352
77. Ayala, Y. M., Zago, P., D'Ambrogio, A., Xu, Y.-F., Petrucelli, L., Buratti, E., and Baralle, F. E. (2008) Structural determinants of the cellular localization and shuttling of TDP-43. J. Cell Sci. 121, 3778-3785
78. Ihara, R., Matsukawa, K., Nagata, Y., Kunugi, H., Tsuji, S., Chihara, T., Kuranaga, E., Miura, M., Wakabayashi, T., Hashimoto, T., and Iwatsubo, T. (2013) RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy. Hum. Mol. Genet. 22, 4474-4484