USP30 特异性切割 Lys6 连接的多泛素链的结构基础。
Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30.
机构信息
Structural Life Science Division, Synchrotron Radiation Research Organization, The University of Tokyo, Tokyo, Japan.
Center for Structural Biology of Challenging Proteins, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
出版信息
Nat Struct Mol Biol. 2017 Nov;24(11):911-919. doi: 10.1038/nsmb.3469. Epub 2017 Sep 25.
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) 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.
Parkin 泛素（Ub）连接酶（也称为 PARK2）泛素化受损的线粒体，以清除和控制其质量。USP30 去泛素酶通过优先切割 Lys6 连接的 Ub 链来拮抗 parkin 介导的线粒体上 Ub 链的形成。在这里，我们报告了斑马鱼 USP30 与 Lys6 连接的二泛素（diUb 或 Ub）复合物的晶体结构，分辨率为 1.87-Å。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 则由 USP30 特异性表面识别。基于结构的突变显示，与近端 Ub 的界面对于 Lys6 连接的 Ub 链的特异性切割至关重要，与由 Cys-His-Ser 组成的非典型催化三联体一起。这里呈现的结构发现揭示了 Lys6 连接特异性去泛素化的机制。
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