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
    • National Institute for Medical ResearchThe Ridgeway
  • Michael Habeck
    • Max-Planck Institutes for Developmental Biology and for Biological Cybernetics
  • Laura Masino
    • National Institute for Medical ResearchThe Ridgeway
  • Dmitri I. Svergun
    • European Molecular Biology Laboratory Hamburg Outstation
    • Institute of CrystallographyRussian Academy of Sciences
    • National Institute for Medical ResearchThe Ridgeway

DOI: 10.1007/s10858-006-9092-z

Cite this article as:
Nicastro, G., Habeck, M., Masino, L. et al. J Biomol NMR (2006) 36: 267. doi:10.1007/s10858-006-9092-z


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.


cysteine proteasepolyglutamine diseaseSCA3structureubiquitinUbl

Copyright information

© Springer Science+Business Media B.V. 2006