Characterization of the conformational fluctuations in the Josephin domain of ataxin-3

Biophys J. 2014 Dec 16;107(12):2932-2940. doi: 10.1016/j.bpj.2014.10.008.

Abstract

As for a variety of other molecular recognition processes, conformational fluctuations play an important role in the cleavage of polyubiquitin chains by the Josephin domain of ataxin-3. The interaction between Josephin and ubiquitin appears to be mediated by the motions of α-helical hairpin that is unusual among deubiquitinating enzymes. Here, we characterized the conformational fluctuations of the helical hairpin by incorporating NMR measurements as replica-averaged restraints in molecular dynamics simulations, and by validating the results by small-angle x-ray scattering measurements. This approach allowed us to define the extent of the helical hairpin motions and suggest a role of such motions in the recognition of ubiquitin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Ataxin-3 / chemistry*
  • Humans
  • Molecular Dynamics Simulation*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry*
  • Scattering, Small Angle
  • X-Ray Diffraction

Substances

  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3