Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30
Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30
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DOI：
10.1038/nsmb.3469
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发表时间：
2017-09
影响因子：
16.8
通讯作者：
Yusuke Sato;K. Okatsu;Y. Saeki;Koji Yamano;N. Matsuda;Ai Kaiho;A. Yamagata;S. Goto‐Ito;M. Ishikawa;Y. Hashimoto;Keiji Tanaka;S. Fukai
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文献类型：
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作者：
Yusuke Sato;K. Okatsu;Y. Saeki;Koji Yamano;N. Matsuda;Ai Kaiho;A. Yamagata;S. Goto‐Ito;M. Ishikawa;Y. Hashimoto;Keiji Tanaka;S. Fukai
泛素连接酶（也被称为PARK2）泛素化破坏线粒体清除和质量控制。USP30去泛素酶通过优先切割lys6连接的Ub链来反对线粒体上帕金森介导的Ub链形成。在这里，我们以1.87-Å分辨率报道了斑马鱼USP30与lys6连接的二泛素（diUb或Ub2）复合物的晶体结构。USP30的远端Ub识别机制与其他USP家族成员相似，而近端Ub的Phe4和Thr12被USP30特异性表面识别。基于结构的突变表明，与近端Ub的界面对于lys6连接的Ub链以及由Cys-His-Ser组成的非规范催化三联体的特异性裂解至关重要。本文提出的结构发现揭示了lys6键特异性去泛素化的机制。
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 Ub2) at 1.87-Å 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.