Crystal Structure of UbcH5b∼Ubiquitin Intermediate: Insight into the Formation of the Self-Assembled E2∼Ub Conjugates
Crystal Structure of UbcH5b∼Ubiquitin Intermediate: Insight into the Formation of the Self-Assembled E2∼Ub Conjugates
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DOI：
10.1016/j.str.2009.11.007
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发表时间：
2010-01-13
期刊：
影响因子：
5.7
通讯作者：
Kato, Koichi
中科院分区：
文献类型：
--
作者：
Sakata, Eri;Satoh, Tadashi;Kato, Koichi
E2泛素结合酶催化泛素与靶蛋白的赖氨酸残基的连接。UbcH5b E2酶已被证明在几种E3连接酶的作用下在底物蛋白的泛素化的起始中起关键作用。在这里，我们已经确定了2.2埃的晶体结构的中间体UbcH5b类似于泛素（Ub）共轭，这是组装成一个无限的螺旋通过背面的相互作用。这种活性复合物可以提供多个E2活性位点，使底物的有效泛素化成为可能。事实上，生物化学分析支持这样一种模型，即自组装的UbcH5 b类似于Ub，可以作为底物的赖氨酸残基和E2的催化半胱氨酸之间的差距的桥梁。
E2 ubiquitin-conjugating enzymes catalyze the attachment of ubiquitin to lysine residues of target proteins. The UbcH5b E2 enzyme has been shown to play a key role in the initiation of the ubiquitination of substrate proteins upon action of several E3 ligases. Here we have determined the 2.2 angstrom crystal structure of an intermediate of UbcH5b similar to ubiquitin (Ub) conjugate, which is assembled into an infinite spiral through the backside interaction. This active complex may provide multiple E2 active sites, enabling efficient ubiquitination of substrates. Indeed, biochemical assays support a model in which the self-assembled UbcH5b similar to Ub can serve as a bridge for the gap between the lysine residue of the substrate and the catalytic cysteine of E2.