DOI: 10.1073/pnas.0506344102. Deubiquitinating function of ataxin-3: Insights from the solution structure of the Josephin domain

Deubiquitinating function of ataxin-3: Insights from the solution structure of the Josephin domain

10.1073/pnas.0506344102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Spinocerebellar ataxia type 3 is a human neurodegenerative disease resulting from polyglutamine tract expansion. The affected protein, ataxin-3, which contains an N-terminal Josephin domain followed by tandem ubiquitin (Ub)-interacting motifs (UIMs) and a polyglutamine stretch, has been implicated in the function of the Ub proteasome system. NMR-based structural analysis has now revealed that the Josephin domain binds Ub and has a papain-like fold that is reminiscent of that of other deubiquitinases, despite primary sequence divergence but consistent with its deubiqutinating activity. Mutation of the catalytic Cys enhances the stability of a complex between ataxin-3 and polyubiquitinated proteins. This effect depends on the integrity of the UIM region, suggesting that the UIMs are bound to the substrate polyubiquitin during catalysis. We propose that ataxin-3 functions as a polyubiquitin chain-editing enzyme.

Bibliography

Mao, Y., Senic-Matuglia, F., Di Fiore, P. P., Polo, S., Hodsdon, M. E., & De Camilli, P. (2005). Deubiquitinating function of ataxin-3: Insights from the solution structure of the Josephin domain. Proceedings of the National Academy of Sciences, 102(36), 12700â12705.

Authors 6

Yuxin Mao (first)
Francesca Senic-Matuglia (additional)
Pier Paolo Di Fiore (additional)
Simona Polo (additional)
Michael E. Hodsdon (additional)
Pietro De Camilli (additional)

References 43 Referenced 137

Iwabuchi, K., Tsuchiya, K., Uchihara, T. & Yagishita, S. (1999) Rev. Neurol. (Paris) 155, 255–270.10367323 / Rev. Neurol. (Paris) (1999)
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Dates

Type	When
Created	20 years ago (Aug. 23, 2005, 10:44 p.m.)
Deposited	1 year, 7 months ago (Jan. 29, 2024, 1:48 a.m.)
Indexed	4 days, 4 hours ago (Sept. 3, 2025, 6:29 a.m.)
Issued	20 years ago (Aug. 23, 2005)
Published	20 years ago (Aug. 23, 2005)
Published Online	20 years ago (Aug. 23, 2005)
Published Print	20 years ago (Sept. 6, 2005)

Funders 0

None

BibTeX

@article{Mao_2005, title={Deubiquitinating function of ataxin-3: Insights from the solution structure of the Josephin domain}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0506344102}, DOI={10.1073/pnas.0506344102}, number={36}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Mao, Yuxin and Senic-Matuglia, Francesca and Di Fiore, Pier Paolo and Polo, Simona and Hodsdon, Michael E. and De Camilli, Pietro}, year={2005}, month=aug, pages={12700–12705} }

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