Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B
Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B
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DOI：
10.1074/jbc.m309448200
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发表时间：
2004-02-06
影响因子：
4.8
通讯作者：
Shirakawa, M
中科院分区：
文献类型：
--
作者：
Fujiwara, K;Tenno, T;Shirakawa, M
泛素化是一种修饰，其中单个或多个泛素分子连接到蛋白质上，具有控制几种细胞过程的信号功能。泛素化信号被下游效应物识别，其中许多效应物携带泛素相互作用基序（UIM）。这种相互作用可以通过携带泛素样（UbL）结构域的调节因子进行调节，该结构域通过模拟泛素化结合UIM。其中，HR23 B调节泛素化底物、DNA修复因子和其他蛋白质的蛋白酶体靶向。在这里，我们报告的结构的UIM的蛋白酶体亚基S5a绑定到UbL域的HR23 B。UbL结构域呈现一个疏水性和两个极性接触位点，用于与UIM相互作用。这些接触位点的残基在泛素中是很保守的，但泛素也在界面处呈现组氨酸。该残基的pH依赖性质子化干扰泛素进入UIM和泛素相关结构域（乌巴），并且其突变为较小的残基增加了泛素对UIM的亲和力。
Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves signaling functions that control several cellular processes. The ubiquitination signal is recognized by downstream effectors, many of which carry a ubiquitin-interacting motif (UIM). Such interactions can be modulated by regulators carrying a ubiquitin-like (UbL) domain, which binds UIM by mimicking ubiquitination. Of them, HR23B regulates the proteasomal targeting of ubiquitinated substrates, DNA repair factors, and other proteins. Here we report the structure of the UIM of the proteasome subunit S5a bound to the UbL domain of HR23B. The UbL domain presents one hydrophobic and two polar contact sites for interaction with UIM. The residues in these contact sites are well conserved in ubiquitin, but ubiquitin also presents a histidine at the interface. The pH-dependent protonation of this residue interferes with the access of ubiquitin to the UIM and the ubiquitin-associated domain (UBA), and its mutation to a smaller residue increases the affinity of ubiquitin for UIM.