Crystal structure of the catalytic domain of UCHL5, a proteasome-associated human deubiquitinating enzyme, reveals an unproductive form of the enzyme.
Crystal structure of the catalytic domain of UCHL5, a proteasome-associated human deubiquitinating enzyme, reveals an unproductive form of the enzyme.
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DOI：
10.1111/j.1742-4658.2011.08393.x
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Das C
中科院分区：
文献类型：
--
作者：
Maiti TK;Permaul M;Boudreaux DA;Mahanic C;Mauney S;Das C
泛素羧基末端水解酶L5（UCHL 5）是一种蛋白酶体相关的去泛素化酶，与RPN 11和USP 14一起沿着对蛋白酶体进行去泛素化。作为UCH家族的一员，UCHL 5是不寻常的，因为与UCHL 1和UCHL 3不同，它可以加工多聚泛素链。然而，它只有在与蛋白酶体结合时才能这样做;在其游离形式下，它只能从泛素的C-末端释放相对较小的离去基团。这样的行为可能表明至少有两种催化不同形式的酶，载脂蛋白的形式不能链加工活性，和蛋白酶体诱导的活化形式能够裂解聚泛素链。通过晶体结构分析的两个截短的结构代表的催化结构域（UCH结构域）的这种酶，我们能够可视化的状态，我们解释为它的非活性形式，因为催化半胱氨酸似乎是在一个非生产性的方向。在这项工作进行的同时，报告了代表UCH结构域的不同结构的结构;然而，在这项工作中，报道结构是一种失活突变体的结构（催化Cys至Ala，西尾K，Kim SW，Kawai K，Mizushima T，Yamane T，Hamazaki J，Murata S，Tanaka K和Morimoto Y（2009）Biochem Biophys Res Commun 390，855-860），这就排除了我们在这里报告的观察结果。此外，我们的结构揭示了酶的构象动态部分，这些部分可能在向更活跃形式的结构转变中发挥作用。
Ubiquitin carboxy-terminal hydrolase L5 (UCHL5) is a proteasome-associated deubiquitinating enzyme, which, along with RPN11 and USP14, is known to carry out deubiquitination on proteasome. As a member of UCH family, UCHL5 is unusual because, unlike UCHL1 and UCHL3, it can process polyubiquitin chain. However, it does so only when it is bound to the proteasome; in its free form, it is capable of releasing only relatively small leaving groups from the C-terminus of ubiquitin. Such a behavior might suggest at least two catalytically distinct forms of the enzyme, an apo form incapable of chain processing activity, and a proteasome-induced activated form capable of cleaving polyubiquitin chain. Through the crystal structure analysis of two truncated constructs representing the catalytic domain (UCH domain) of this enzyme, we are able to visualize a state of this enzyme that we interpret as its inactive form, because the catalytic cysteine appears to be in an unproductive orientation. While this work was in progress, the structure of a different construct representing the UCH domain was reported; however, in that work the structure reported was that of an inactive mutant (catalytic Cys to Ala, Nishio K, Kim SW, Kawai K, Mizushima T, Yamane T, Hamazaki J, Murata S, Tanaka K and Morimoto Y (2009) Biochem Biophys Res Commun 390, 855-860), which precluded the observation that we are reporting here. Additionally, our structures reveal conformationally dynamic parts of the enzyme that may play a role in the structural transition to the more active form.
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DOI：
10.1074/mcp.r110.003871
发表时间：
2011-05-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Lee, Min Jae;Lee, Byung-Hoon;Finley, Daniel
通讯作者：
Finley, Daniel
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
16.6
作者：
Finley D
通讯作者：
Finley D
影响因子：
11.4
作者：
Johnston, SC;Riddle, SM;Hill, CP
通讯作者：
Hill, CP
影响因子：
4.8
作者：
Misaghi, S;Galardy, PJ;Gaudet, R
通讯作者：
Gaudet, R