Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1
Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1
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DOI：
10.1038/sj.emboj.7600552
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发表时间：
2005-02-09
期刊：
影响因子：
11.4
通讯作者：
Lima, CD
中科院分区：
文献类型：
--
作者：
Lois, LM;Lima, CD
E1酶通过腺化作用促进泛素和泛素样蛋白的结合，在E1内进行硫酯转移，并将硫酯从E1结合蛋白转移到E2结合蛋白。人异二聚体Sae1/Sae2-mg.ATP和Sae1/Sae2-相扑-1-mg。ATP络合物的测定分辨率分别为2.2埃和2.75埃。尽管有镁的存在。三磷酸腺苷，Sae1/Sae2-相扑-1 mg。ATP结构揭示了底物复合体，如相扑C末端在腺化位点和催化半胱氨酸的35埃处保持不变，这表明在腺基化和硫酯转移之前，腺基化位点可能需要额外的变化来促进化学作用。生化和遗传数据表明了一种E2募集到E1的机制，每一种机制都支持在接合过程中E1C末端的泛素样结构域直接作用于E2募集。
E1 enzymes facilitate conjugation of ubiquitin and ubiquitin-like proteins through adenylation, thioester transfer within E1, and thioester transfer from E1 to E2 conjugating proteins. Structures of human heterodimeric Sae1/Sae2-Mg. ATP and Sae1/Sae2-SUMO-1-Mg. ATP complexes were determined at 2.2 and 2.75 Angstrom resolution, respectively. Despite the presence of Mg. ATP, the Sae1/Sae2-SUMO-1Mg. ATP structure reveals a substrate complex insomuch as the SUMO C-terminus remains unmodified within the adenylation site and 35 Angstrom from the catalytic cysteine, suggesting that additional changes within the adenylation site may be required to facilitate chemistry prior to adenylation and thioester transfer. A mechanism for E2 recruitment to E1 is suggested by biochemical and genetic data, each of which supports a direct role for the E1 C-terminal ubiquitin-like domain for E2 recruitment during conjugation.