Defining the geometry of the two-component proteasome degron.
Defining the geometry of the two-component proteasome degron.
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DOI：
10.1038/nchembio.521
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发表时间：
2011-03
影响因子：
14.8
通讯作者：
Matouschek, Andreas
中科院分区：
文献类型：
--
作者：
Inobe, Tomonao;Fishbain, Susan;Prakash, Sumit;Matouschek, Andreas
真核26S蛋白酶体通过降解特定的调节蛋白来控制细胞过程。大多数蛋白质都是通过信号或降解子降解的目标，该信号或降解子由两部分组成：蛋白酶体结合标签，通常是共价连接的多泛素链，以及作为蛋白酶体蛋白水解起始区域的非结构化区域。在这里，我们描述了蛋白质中两个降解部分的排列如何影响降解。我们发现，只有当底物的起始区具有一定的最小长度并在空间上与蛋白酶体结合标签适当分离时，底物才能有效降解。离蛋白酶体结合标签太近或太远的区域不能进入蛋白酶体并诱导降解。这些间距要求对于泛素链和泛素样结构域是不同的。因此，蛋白酶体起始区域的排列和位置影响蛋白质的命运，并在选择蛋白酶体介导降解的蛋白质中发挥核心作用。
The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the initiation region for proteasomal proteolysis. Here we have characterized how the arrangement of the two degron parts in a protein affects degradation. We found that a substrate is degraded efficiently only when its initiation region is of a certain minimal length and is appropriately separated in space from the proteasome-binding tag. Regions that are located too close or too far from the proteasome-binding tag cannot access the proteasome and induce degradation. These spacing requirements are different for a polyubiquitin chain and a ubiquitin-like (UbL) domain. Thus, arrangement and location of the proteasome initiation region affect a protein’s fate and play a central role in selecting proteins for proteasome-mediated degradation.
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影响因子：
64.5
作者：
HOCHSTRASSER, M;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
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作者：
JOHNSON, ES;GONDA, DK;VARSHAVSKY, A
通讯作者：
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