An unstructured initiation site is required for efficient proteasome-mediated degradation
An unstructured initiation site is required for efficient proteasome-mediated degradation
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DOI：
10.1038/nsmb814
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发表时间：
2004-09-01
影响因子：
16.8
通讯作者：
Matouschek, A
中科院分区：
文献类型：
--
作者：
Prakash, S;Tian, L;Matouschek, A
蛋白酶体是真核细胞中主要的ATP依赖性蛋白酶，控制着细胞质和细胞核中许多调节蛋白的浓度。蛋白质通过多聚泛素链的共价连接靶向蛋白酶体。泛素修饰作为蛋白酶体识别元件，但其本身不足以有效降解折叠蛋白。我们报告说，蛋白质水解的紧密折叠的蛋白质大大加速时，非结构化区域连接到基板。非结构化区域作为降解的起始位点，首先水解，然后依次消化其余蛋白质。这些结果将起始位点鉴定为靶向信号的新组分，这是有效地参与蛋白酶体解折叠机制所需的。蛋白酶体通过首先结合其泛素修饰，然后在非结构化区域开始解折叠来降解底物。
The proteasome is the main ATP-dependent protease in eukaryotic cells and controls the concentration of many regulatory proteins in the cytosol and nucleus. Proteins are targeted to the proteasome by the covalent attachment of polyubiquitin chains. The ubiquitin modification serves as the proteasome recognition element but by itself is not sufficient for efficient degradation of folded proteins. We report that proteolysis of tightly folded proteins is accelerated greatly when an unstructured region is attached to the substrate. The unstructured region serves as the initiation site for degradation and is hydrolyzed first, after which the rest of the protein is digested sequentially. These results identify the initiation site as a novel component of the targeting signal, which is required to engage the proteasome unfolding machinery efficiently. The proteasome degrades a substrate by first binding to its ubiquitin modification and then initiating unfolding at an unstructured region.