Solution structure of the human ubiquitin-specific protease 15 DUSP domain
Solution structure of the human ubiquitin-specific protease 15 DUSP domain
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DOI：
10.1074/jbc.m510993200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Folkers, GE
中科院分区：
文献类型：
--
作者：
de Jong, RN;Ab, E;Folkers, GE
泛素特异性蛋白酶（USP）可以从靶蛋白上去除共价连接的泛素部分，并调节其底物的稳定性和泛素信号状态。所有USP都含有一个保守的催化结构域，周围有一个或多个亚结构域，其中一些有助于靶点识别。一个这样的特定亚结构域，即DUSP结构域（存在于遍在蛋白特异性蛋白酶中的结构域），存在于至少七种不同的人类USP中，它们调节缺氧诱导型转录因子HIF 1-alpha、Von Hippel-Lindau蛋白（pVHL）、cullin E3连接酶和BRCA 2的稳定性或与之相互作用。我们描述的NMR溶液结构的DUSP结构域的人USP 15，最近牵连在COP 9（组成型光形态发生基因9）-信号体调节。它的三脚架样结构由3倍α-螺旋束支撑三链反平行α-片层组成。DUSP结构域显示了一种新的折叠，α/β三脚架（AB 3）。DUSP结构域表面性质和先前描述的工作表明在蛋白质/蛋白质相互作用或底物识别中的潜在作用。
Ubiquitin-specific proteases ( USPs) can remove covalently attached ubiquitin moieties from target proteins and regulate both the stability and ubiquitin-signaling state of their substrates. All USPs contain a conserved catalytic domain surrounded by one or more subdomains, some of which contribute to target recognition. One such specific subdomain, the DUSP domain ( domain present in ubiquitin-specific proteases), is present in at least seven different human USPs that regulate the stability of or interact with the hypoxia-inducible transcription factor HIF1-alpha, the Von Hippel-Lindau protein ( pVHL), cullin E3 ligases, and BRCA2. We describe the NMR solution structure of the DUSP domain of human USP15, recently implicated in COP9 ( constitutive photomorphogenic gene 9) -signalosome regulation. Its tripod-like structure consists of a 3-fold alpha-helical bundle supporting a triple-stranded anti-parallel alpha-sheet. The DUSP domain displays a novel fold, an alpha/beta tripod ( AB3). DUSP domain surface properties and previously described work suggest a potential role in protein/protein interaction or substrate recognition.