کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2047552 | 1073989 | 2014 | 9 صفحه PDF | دانلود رایگان |
• The Josephin domain of ataxin-3 acts as an endo-type deubiquitinase.
• NMR data revealed that the Josephin domain has multiple ubiquitin-binding sites.
• Structural basis is provided for the endo-type deubiquitination mechanism.
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.
Journal: FEBS Letters - Volume 588, Issue 23, 28 November 2014, Pages 4422–4430