Journal of Biomolecular NMR

, Volume 36, Issue 4, pp 267–277

Structure validation of the Josephin domain of ataxin-3: Conclusive evidence for an open conformation

  • Giuseppe Nicastro
  • Michael Habeck
  • Laura Masino
  • Dmitri I. Svergun
  • Annalisa Pastore
Article

Abstract

The availability of new and fast tools in structure determination has led to a more than exponential growth of the number of structures solved per year. It is therefore increasingly essential to assess the accuracy of the new structures by reliable approaches able to assist validation. Here, we discuss a specific example in which the use of different complementary techniques, which include Bayesian methods and small angle scattering, resulted essential for validating the two currently available structures of the Josephin domain of ataxin-3, a protein involved in the ubiquitin/proteasome pathway and responsible for neurodegenerative spinocerebellar ataxia of type 3. Taken together, our results demonstrate that only one of the two structures is compatible with the experimental information. Based on the high precision of our refined structure, we show that Josephin contains an open cleft which could be directly implicated in the interaction with polyubiquitin chains and other partners.

Keywords

cysteine protease polyglutamine disease SCA3 structure ubiquitin Ubl 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bax A. (2003) Protein Sci., 12:1–16CrossRefGoogle Scholar
  2. Boulin C.J., Kempf R., Gabriel A., Koch M.H.J. (1988) Nucl. Instrum. Meth. A, 269:312–320CrossRefADSGoogle Scholar
  3. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-unstleve R.W., et al. (1998) Acta Crystallog. Sect. D, 54:905–921CrossRefGoogle Scholar
  4. Burnett B., Li F., Pittman R.N. (2003) Hum. Mol. Genet., 12:3195–3205CrossRefGoogle Scholar
  5. Chai Y., Berke S.S., Cohen R.E., Paulson H.L. (2004) J. Biol. Chem., 279:3605–3611CrossRefGoogle Scholar
  6. Donaldson K.M., Li W., Ching K.A., Batalov S., Tsai C.C., Joazeiro C.A. (2003) Proc. Natl. Acad. Sci. USA, 100:8892–8897CrossRefADSGoogle Scholar
  7. Gabriel A., Dauvergne F. (1982) Nucl. Instrum. Meth., 201:223–224CrossRefGoogle Scholar
  8. Habeck M., Nilges M., Rieping W. (2005a) Phys. Rev. E. Stat. Nonlin. Soft Matter Phys., 72:031912ADSGoogle Scholar
  9. Habeck M., Nilges M., Rieping W. (2005b) Phys. Rev. Lett., 94:018105CrossRefADSGoogle Scholar
  10. Habeck M., Rieping W., Nilges M. (2006) Proc. Natl. Acad. Sci. USA, 103:1756–1761CrossRefADSGoogle Scholar
  11. Johnston S.C., Riddle S.M., Cohen R.E., Hill C.P. (1999) EMBO J., 18:3877–3887CrossRefGoogle Scholar
  12. Kawaguchi Y., Okamoto T., Taniwaki M., Aizawa M., Inoue M., Katayama S., Kawakami H., Nakamura S., Nishimura M., Akiguchi I., et al. (1994) Nat. Genet., 8:221–228CrossRefGoogle Scholar
  13. Koch M.H.J., Bordas J. (1983) Nucl. Instrum. Methods, 208:461–469CrossRefGoogle Scholar
  14. Konarev P.V., Volkov V.V., Sokolova A.V., Koch M.H.J., Svergun D.I. (2003) J. Appl. Crystallogr., 36:1277–1282CrossRefGoogle Scholar
  15. Kozin M.B., Svergun D.I. (2001) J. Appl. Crystallogr., 34:33–41CrossRefGoogle Scholar
  16. Laskowski R.A., Rullmannn J.A., MacArthur M.W., Kaptein R., Thornton J.M. (1996) J. Biomol. NMR, 8:477–486CrossRefGoogle Scholar
  17. Masino L, Nicastro G, Menon RP, Dal Piaz F, Calder L., Pastore A. (2004) J. Mol Biol., 344:1021–1035CrossRefGoogle Scholar
  18. Masino L., Musi V., Menon R.P., Fusi P., Kelly G., Frenkiel T.A., Trottier Y., Pastore A. (2003) FEBS Lett., 549:21–25CrossRefGoogle Scholar
  19. Mao Y., Senic-Matuglia F, Di Fiore P.P., Polo S., Hodsdon M.E., De Camilli P. (2005) Proc. Natl. Acad. Sci. USA, 102:12700–12705CrossRefADSGoogle Scholar
  20. Munishkina L.A., Cooper E.M., Uversky V.N., Fink A.L. (2004) J. Mol. Recognit., 17:456–464CrossRefGoogle Scholar
  21. Nicastro G., Menon R.P., Masino L, Knowles P.P., McDonald N.Q., Pastore A. (2005) Proc. Natl. Acad. Sci. USA, 102:10493–10498CrossRefADSGoogle Scholar
  22. Nicastro G., Masino L., Frenkiel T.A., Kelly G., McCormick J., Menon R.P., Pastore A. (2004) J. Biomol. NMR, 30:457–458CrossRefGoogle Scholar
  23. Porod, G. (1982) In Small-angle X-ray scattering, Glatter, O. and Kratky, O. (Eds.), Academic Press, London, pp. 17–51Google Scholar
  24. Rieping W., Habeck M., Nilges M. (2005a) Science, 309:303–306CrossRefADSGoogle Scholar
  25. Rieping W., Habeck M., Nilges M. (2005b) J. Am. Chem. Soc., 127:16026–16027CrossRefGoogle Scholar
  26. Sass H.J., Musco G., Stahl S.J., Wingfield P.T., Grzesiek S. (2000) J. Biomol. NMR, 18:303–309CrossRefGoogle Scholar
  27. Svergun D.I. (1992) J. Appl. Crystallogr., 25:495–503CrossRefGoogle Scholar
  28. Svergun D.I. (1999) Biophys. J., 76:2879–2886CrossRefGoogle Scholar
  29. Svergun D.I., Koch M.H.J. (2003) Rep. Progr. Phys., 66:1735–1782CrossRefADSGoogle Scholar
  30. Svergun D.I., Barberato C., Koch M.H.J. (1995) J. Appl. Crystallogr., 28:768–773CrossRefGoogle Scholar
  31. Svergun D.I., Petoukhov M.V., M.H.J. Koch M.H.J. (2001) Biophys. J., 80:2946–2953Google Scholar
  32. Taylor J.P., Hardy J., Fischbeck K.H. (2002) Science, 296:1991–1995CrossRefADSGoogle Scholar
  33. Vestergaard B., Sanyal S., Roessle M., Mora L., Buckingham R.H., Kastrup J.S., Gajhede M., Svergun D.I., Ehrenberg M. (2005) Mol. Cell, 20:929–938CrossRefGoogle Scholar
  34. Volkov V.V., Svergun D.I. (2003) J. Appl. Crystallogr., 36:860–864CrossRefGoogle Scholar
  35. Vriend G. (1990) J. Mol. Graph., 8:52–56CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Giuseppe Nicastro
    • 1
  • Michael Habeck
    • 2
  • Laura Masino
    • 1
  • Dmitri I. Svergun
    • 3
    • 4
  • Annalisa Pastore
    • 1
  1. 1.National Institute for Medical ResearchThe RidgewayLondonUK
  2. 2.Max-Planck Institutes for Developmental Biology and for Biological CyberneticsTübingenGermany
  3. 3.European Molecular Biology Laboratory Hamburg OutstationHamburgGermany
  4. 4.Institute of CrystallographyRussian Academy of SciencesMoscowRussia

Personalised recommendations