Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB-MoaD complex
Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB-MoaD complex
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DOI：
10.1038/35104586
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发表时间：
2001-11-15
期刊：
影响因子：
64.8
通讯作者：
Schindelin, H
中科院分区：
文献类型：
--
作者：
Lake, MW;Wuebbens, MM;Schindelin, H
泛素和相关蛋白质修饰剂 (1,2) 的激活由 E1 酶家族成员催化，这些成员使用 ATP 将修饰剂共价自附着到保守的半胱氨酸上。大肠杆菌蛋白 MoeB 和 MoaD 参与钼辅因子 (Moco) 生物合成，这是一条进化上保守的途径 (3,4)。 MoeB 和 E1 催化的反应在机制上相似，尽管缺乏序列相似性，MoaD 和泛素却显示出相同的折叠，包括保守的羧基末端 Gly-Gly 基序 (5)。与 E1 酶类似，MoeB 激活 MoaD 的 C 末端形成酰基腺苷酸。随后，硫转移酶将 MoaD 酰基腺苷酸转化为硫代羧酸盐，在 Moco 生物合成过程中充当硫供体 (6,7)。这些发现表明，泛素和 E1 源自与 moaD 和 moeB (3,5) 密切相关的两个祖先基因。在这里，我们展示了 MoeB-MoaD 复合物的 apo、ATP 结合和 MoaD-腺苷酸形式的晶体结构，并强调了 MoeB-和 E1-底物复合物之间的功能相似性。这些结构为理解 Moco 和硫胺素生物合成过程中泛素、Rub、SUMO 的激活以及硫掺入步骤提供了分子框架。
The activation of ubiquitin and related protein modifiers(1,2) is catalysed by members of the E1 enzyme family that use ATP for the covalent self-attachment of the modifiers to a conserved cysteine. The Escherichia coli proteins MoeB and MoaD are involved in molybdenum cofactor (Moco) biosynthesis, an evolutionarily conserved pathway(3,4). The MoeB- and E1-catalysed reactions are mechanistically similar, and despite a lack of sequence similarity, MoaD and ubiquitin display the same fold including a conserved carboxy-terminal Gly-Gly motif(5). Similar to the E1 enzymes, MoeB activates the C terminus of MoaD to form an acyl-adenylate. Subsequently, a sulphurtransferase converts the MoaD acyl-adenylate to a thiocarboxylate that acts as the sulphur donor during Moco biosynthesis(6,7). These findings suggest that ubiquitin and E1 are derived from two ancestral genes closely related to moaD and moeB(3,5). Here we present the crystal structures of the MoeB-MoaD complex in its apo, ATP-bound, and MoaD-adenylate forms, and highlight the functional similarities between the MoeB- and E1-substrate complexes. These structures provide a molecular framework for understanding the activation of ubiquitin, Rub, SUMO and the sulphur incorporation step during Moco and thiamine biosynthesis.