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.

中文翻译：

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USP30特异性裂解Lys6连接的聚泛素链的结构基础

Parkin泛素（Ub）连接酶（也称为PARK2）可泛素化损伤的线粒体，以进行清除和质量控制。USP30去泛素化酶通过优先裂解Lys6连接的Ub链，反对线粒体上的Parkin介导的Ub链形成。在这里，我们报告斑马鱼USP30的晶体结构与Lys6连接的双泛素（diUb或Ub ₂）的分辨率为1.87-Å。USP30的远端Ub识别机制与其他USP家族成员的机制相似，而近端Ub的Phe4和Thr12被USP30特异性表面识别。基于结构的诱变表明，与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，与近端Ub的界面至关重要。这里介绍的结构发现揭示了Lys6连锁特异性去泛素化的机制。