Mode of substrate recognition by the Josephin domain of ataxin-3, which has an endo-type deubiquitinase activity

Tadashi Satoh, Akira Sumiyoshi, Maho Yagi-Utsumi, Eri Sakata, Hiroaki Sasakawa, Eiji Kurimoto, Yoshiki Yamaguchi, Wei Li, Claudio A.P. Joazeiro, Takatsugu Hirokawa, Koichi Kato

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Ataxin-3, which is encoded by a gene that has been associated with Machado-Joseph disease, contains a catalytic N-terminal Josephin domain with deubiquitinase activity. Here, we show that the Josephin domain of ataxin 3 catalyzes endo-type cleavage of Lys48-linked polyubiquitin. Furthermore, NMR data obtained following site-specific paramagnetic spin labeling of Lys48-linked di-ubiquitin revealed that both ubiquitin units interact with the Josephin domain, with the C-terminal Gly76 of the proximal unit being situated in the vicinity of the catalytic triad of Josephin domain. Our results help to elucidate how the substrate is recognized by the Josephin domain and properly positioned for an endo-type deubiquitination reaction.

Original languageEnglish
Pages (from-to)4422-4430
Number of pages9
JournalFEBS Letters
Volume588
Issue number23
DOIs
Publication statusPublished - 2014 Nov 28

Keywords

  • Ataxin-3
  • Deubiquitinase
  • Josephin domain
  • Molecular docking simulation
  • NMR spectroscopy

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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