A family of unconventional deubiquitinases with modular chain specificity determinants.
A family of unconventional deubiquitinases with modular chain specificity determinants.
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DOI：
10.1038/s41467-018-03148-5
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发表时间：
2018-02-23
影响因子：
16.6
通讯作者：
Hofmann K
中科院分区：
文献类型：
--
作者：
Hermanns T;Pichlo C;Woiwode I;Klopffleisch K;Witting KF;Ovaa H;Baumann U;Hofmann K
去泛素化酶（DUBs）通过修剪泛素链或从修饰底物中去除泛素来调节泛素信号。类似的活性存在于泛素相关的修饰剂，尽管所涉及的酶通常不相关。在这里，我们报告了人类ZUFSP（也称为ZUP1和C6orf113）和裂变酵母Mug105作为DUB家族的创始成员，不同于已知的六个DUB类。人ZUFSP与丙基化泛素共价复合物的晶体结构表明，DUB家族与UFM1-和atg8特异性蛋白酶共享一个折叠，但使用与典型DUB酶更相似的不同活性位点。通过模块化泛素结合域（UBDs）的不同使用，ZUFSP家族成员在连锁特异性上存在很大差异。虽然简约的Mug105更喜欢K48链，但ZUFSP使用多个ubd来实现其k63特异性的内- dub活性。K63特异性、定位和蛋白相互作用网络提示ZUFSP在DNA损伤应答中发挥作用。去泛素化酶（DUBs）是调节泛素信号的关键。虽然已知的DUB可以分为六个家族，但作者在这里提出了第七个DUB家族的生化和结构证据，确定了两种代表性酶的底物特异性决定因素。
Deubiquitinating enzymes (DUBs) regulate ubiquitin signaling by trimming ubiquitin chains or removing ubiquitin from modified substrates. Similar activities exist for ubiquitin-related modifiers, although the enzymes involved are usually not related. Here, we report human ZUFSP (also known as ZUP1 and C6orf113) and fission yeast Mug105 as founding members of a DUB family different from the six known DUB classes. The crystal structure of human ZUFSP in covalent complex with propargylated ubiquitin shows that the DUB family shares a fold with UFM1- and Atg8-specific proteases, but uses a different active site more similar to canonical DUB enzymes. ZUFSP family members differ widely in linkage specificity through differential use of modular ubiquitin-binding domains (UBDs). While the minimalistic Mug105 prefers K48 chains, ZUFSP uses multiple UBDs for its K63-specific endo-DUB activity. K63 specificity, localization, and protein interaction network suggest a role for ZUFSP in DNA damage response. Deubiquitinating enzymes (DUBs) are essential to modulate ubiquitin signaling. While known DUBs can be grouped into six families, the authors here present biochemical and structural evidence for a seventh DUB family, defining determinants of substrate specificity for two representative enzymes.
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DOI：
10.1107/s0907444909029436
发表时间：
2009-10-01
影响因子：
2.2
作者：
Moriarty, Nigel W.;Grosse-Kunstleve, Ralf W.;Adams, Paul D.
通讯作者：
Adams, Paul D.
影响因子：
1.6
作者：
Ikebe, Chiho;Konishi, Manabu;Toda, Takashi
通讯作者：
Toda, Takashi
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.5
作者：
Miralles Fusté J;Shi Y;Wanrooij S;Zhu X;Jemt E;Persson Ö;Sabouri N;Gustafsson CM;Falkenberg M
通讯作者：
Falkenberg M
影响因子：
4.8
作者：
Kang, Sung Hwan;Kim, Gi Ryang;Chung, Chin Ha
通讯作者：
Chung, Chin Ha