Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains

PLoS One. 2010 Oct 7;5(10):e13202. doi: 10.1371/journal.pone.0013202.

Abstract

The ubiquitin-interacting motif (UIM) is a short peptide with dual function of binding ubiquitin (Ub) and promoting ubiquitination. We elucidated the structures and dynamics of the tandem UIMs of ataxin-3 (AT3-UIM12) both in free and Ub-bound forms. The solution structure of free AT3-UIM12 consists of two α-helices and a flexible linker, whereas that of the Ub-bound form is much more compact with hydrophobic contacts between the two helices. NMR dynamics indicates that the flexible linker becomes rigid when AT3-UIM12 binds with Ub. Isothermal titration calorimetry and NMR titration demonstrate that AT3-UIM12 binds diUb with two distinct affinities, and the linker plays a critical role in association of the two helices in diUb binding. These results provide an implication that the tandem UIM12 interacts with Ub or diUb in a cooperative manner through an allosteric effect and dynamics change of the linker region, which might be related to its recognitions with various Ub chains and ubiquitinated substrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-3
  • Models, Molecular
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Ubiquitin / metabolism*

Substances

  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Ubiquitin
  • ATXN3 protein, human
  • Ataxin-3