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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Satoh T,Sumiyoshi A,Yagi-Utsumi M,Sakata E,Sasakawa H,Kurimoto E,Yamaguchi Y,Li W,Joazeiro CA,Hirokawa T,Kato K

doi

10.1016/j.febslet.2014.10.013

subject

Has Abstract

pub_date

2014-11-28 00:00:00

pages

4422-30

issue

23

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(14)00748-0

journal_volume

588

pub_type

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