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 language | English |
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Pages (from-to) | 4422-4430 |
Number of pages | 9 |
Journal | FEBS Letters |
Volume | 588 |
Issue number | 23 |
DOIs | |
Publication status | Published - 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