Department of Structural Biology and Biomolecular Engineering, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Structure. 2010 Jan 13;18(1):138-47. doi: 10.1016/j.str.2009.11.007.
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 A crystal structure of an intermediate of UbcH5bubiquitin (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 UbcH5bUb can serve as a bridge for the gap between the lysine residue of the substrate and the catalytic cysteine of E2.
E2 泛素连接酶催化泛素与靶蛋白赖氨酸残基的连接。已经表明，UbcH5b E2 酶在几种 E3 连接酶的作用下，在底物蛋白泛素化的起始中发挥关键作用。在这里，我们确定了 UbcH5b泛素（Ub）缀合物的中间产物的 2.2Å 晶体结构，该结构通过背面相互作用组装成无限螺旋。这个活性复合物可能提供多个 E2 活性位点，从而能够有效地对底物进行泛素化。事实上，生化分析支持这样一种模型，即自组装的 UbcH5bUb 可以作为底物赖氨酸残基和 E2 催化半胱氨酸之间的间隙的桥梁。
