@article{f4b8590e900a4b73a1f9a7f8cce4bc2c,
title = "Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30",
abstract = "Parkin ubiquitin (Ub) ligase (also known as PARK2) ubiquitinates damaged mitochondria for their clearance and quality control. USP30 deubiquitinase opposes parkin-mediated Ub-chain formation on mitochondria by preferentially cleaving Lys6-linked Ub chains. Here, we report the crystal structure of zebrafish USP30 in complex with a Lys6-linked diubiquitin (diUb or Ub 2) at 1.87-{\AA} resolution. The distal Ub-recognition mechanism of USP30 is similar to those of other USP family members, whereas Phe4 and Thr12 of the proximal Ub are recognized by a USP30-specific surface. Structure-based mutagenesis showed that the interface with the proximal Ub is critical for the specific cleavage of Lys6-linked Ub chains, together with the noncanonical catalytic triad composed of Cys-His-Ser. The structural findings presented here reveal a mechanism for Lys6-linkage-specific deubiquitination.",
author = "Yusuke Sato and Kei Okatsu and Yasushi Saeki and Koji Yamano and Noriyuki Matsuda and Ai Kaiho and Atsushi Yamagata and Sakurako Goto-Ito and Minoru Ishikawa and Yuichi Hashimoto and Keiji Tanaka and Shuya Fukai",
note = "Funding Information: We thank J. Chen (Rockefeller University) for providing the NleL plasmid. We thank K. Iwai (Kyoto University) for providing the Ub and E2-25K plasmids. We thank the beamline staff of the biological crystallography beamlines of Photon Factory (Tsukuba, Japan) and BL41XU of SPring-8 (Hyogo, Japan) for technical help during data collection. This work was supported by JSPS/MEXT KAKENHI (JP24687012, JP15H01175 and JP16H04750 to Y. Sato, JP15J10559 to K.O., JP24112008 to Y. Saeki, JP16K18545 to K.Y., JP26000014 to K.T. and JP24247014 to S.F.), JST PRESTO (to N.M.), Takeda Science Foundation (to N.M. and K.T.), the Chieko Iwanaga Fund for Parkinson{\textquoteright}s Disease Research (to N.M.) and JST CREST (JPMJCR12M5 to S.F.). Publisher Copyright: {\textcopyright} 2017 Nature America, Inc., part of Springer Nature. All rights reserved.",
year = "2017",
month = nov,
day = "1",
doi = "10.1038/nsmb.3469",
language = "English",
volume = "24",
pages = "911--919",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "11",
}