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

doi:10.1016/j.febslet.2014.10.013

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

Division of Brain Science

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	4422-4430
Number of pages	9
Journal	FEBS Letters
Volume	588
Issue number	23
DOIs	https://doi.org/10.1016/j.febslet.2014.10.013
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

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Mode of substrate recognition by the Josephin domain of ataxin-3, which has an endo-type deubiquitinase activity. / Satoh, Tadashi; Sumiyoshi, Akira; Yagi-Utsumi, Maho; Sakata, Eri; Sasakawa, Hiroaki; Kurimoto, Eiji; Yamaguchi, Yoshiki; Li, Wei; Joazeiro, Claudio A.P.; Hirokawa, Takatsugu; Kato, Koichi.

In: FEBS Letters, Vol. 588, No. 23, 28.11.2014, p. 4422-4430.

Research output: Contribution to journal › Article › peer-review

Satoh, Tadashi ; Sumiyoshi, Akira ; Yagi-Utsumi, Maho ; Sakata, Eri ; Sasakawa, Hiroaki ; Kurimoto, Eiji ; Yamaguchi, Yoshiki ; Li, Wei ; Joazeiro, Claudio A.P. ; Hirokawa, Takatsugu ; Kato, Koichi. / Mode of substrate recognition by the Josephin domain of ataxin-3, which has an endo-type deubiquitinase activity. In: FEBS Letters. 2014 ; Vol. 588, No. 23. pp. 4422-4430.

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

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.",

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

note = "Funding Information: Expression constructs of E1 and E2-25K were kindly provided from Drs. Yasushi Saeki and Keiji Tanaka (Tokyo Metropolitan Institute of Medical Science). We also thank Drs. Masashi Yokochi and Fuyuhiko Inagaki (Hokkaido University) for providing Olivia version 1.14.0 software. This work was supported in part by JSPS KAKENHI ( 25102008 to K.K.), by the Okazaki ORION project, by the Nanotechnology Platform Project, and by Platform for Drug Discovery, Informatics, and Structural Life Science ( 1274-2 to K.K.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan . ",

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AU - Yagi-Utsumi, Maho

AU - Sakata, Eri

AU - Sasakawa, Hiroaki

AU - Kurimoto, Eiji

AU - Yamaguchi, Yoshiki

AU - Li, Wei

AU - Joazeiro, Claudio A.P.

AU - Hirokawa, Takatsugu

AU - Kato, Koichi

N1 - Funding Information: Expression constructs of E1 and E2-25K were kindly provided from Drs. Yasushi Saeki and Keiji Tanaka (Tokyo Metropolitan Institute of Medical Science). We also thank Drs. Masashi Yokochi and Fuyuhiko Inagaki (Hokkaido University) for providing Olivia version 1.14.0 software. This work was supported in part by JSPS KAKENHI ( 25102008 to K.K.), by the Okazaki ORION project, by the Nanotechnology Platform Project, and by Platform for Drug Discovery, Informatics, and Structural Life Science ( 1274-2 to K.K.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan .

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Y1 - 2014/11/28

N2 - 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.

AB - 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.

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