A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier
A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier
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DOI：
10.1038/sj.emboj.7600205
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发表时间：
2004-05-05
期刊：
影响因子：
11.4
通讯作者：
Tanaka, K
中科院分区：
文献类型：
--
作者：
Komatsu, M;Chiba, T;Tanaka, K
一些研究已经解决了各种泛素样（UBL）翻译后修饰的重要性。这些UBL通过类似于泛素化的酶级联反应与大多数（如果不是全部）靶蛋白共价连接，该酶级联反应由E1（激活）、E2（缀合）和E3（连接）酶组成。在这份报告中，我们描述了一种新的泛素折叠修饰剂1（UFM 1）的分子量为9.1 kDa的鉴定，显示明显相似的三级结构，虽然缺乏明显的序列同一性，泛素。Ufm 1首先在C-末端被切割以暴露其保守的Gly残基。该Gly残基对于其随后的缀合反应是必需的。C-末端加工的Ufm 1被一种新的E1样酶Uba 5激活，形成高能硫酯键。然后将激活的Ufm 1以类似的硫酯键转移到其同源的E2样酶Ufc 1上。Ufm 1在HEK 293细胞和小鼠组织中形成几种复合物，表明它与靶蛋白缀合。Ufm 1、Uba 5和Ufc 1在后生动物和植物中都是保守的，但在酵母中不存在，这表明它在各种多细胞生物中具有潜在的作用。
Several studies have addressed the importance of various ubiquitin-like (UBL) post-translational modifiers. These UBLs are covalently linked to most, if not all, target protein(s) through an enzymatic cascade analogous to ubiquitylation, consisting of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. In this report, we describe the identification of a novel ubiquitin-fold modifier 1 (Ufm1) with a molecular mass of 9.1 kDa, displaying apparently similar tertiary structure, although lacking obvious sequence identity, to ubiquitin. Ufm1 is first cleaved at the C-terminus to expose its conserved Gly residue. This Gly residue is essential for its subsequent conjugating reactions. The C-terminally processed Ufm1 is activated by a novel E1-like enzyme, Uba5, by forming a high-energy thioester bond. Activated Ufm1 is then transferred to its cognate E2-like enzyme, Ufc1, in a similar thioester linkage. Ufm1 forms several complexes in HEK293 cells and mouse tissues, revealing that it conjugates to the target proteins. Ufm1, Uba5, and Ufc1 are all conserved in metazoa and plants but not in yeast, suggesting its potential roles in various multicellular organisms.