Ubc9 sumoylation regulates SUMO target discrimination
Ubc9 sumoylation regulates SUMO target discrimination
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DOI：
10.1016/j.molcel.2008.05.022
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发表时间：
2008-08-08
期刊：
影响因子：
16
通讯作者：
Pichler, Andrea
中科院分区：
文献类型：
--
作者：
Knipscheer, Puck;Flotho, Annette;Pichler, Andrea
用泛素相关的小修饰物SUMO进行翻译后修饰是蛋白质功能快速和可逆变化的一种普遍机制。考虑到大量的已知靶点，参与修饰的酶的数量似乎令人惊讶地低：单一的EL，单一的E2，和一些不同的E3连接酶。在这里，我们证明了哺乳动物E2结合酶Ubc9在Lys14处的自动苏氨酸化调节靶标识别。Ubc9对HDAC4、E2-25K、PML或TDG的活性没有改变，但Ubc9对RanGAP1的活性减弱，并强烈激活转录调节因子Sp100的总和作用。增强依赖于Sp100中的相扑相互作用基序(SIM)，该基序创建与E2共轭的相扑额外界面，这是一种不同于Ubc9的机制，类似于相扑硫酯招募。SUMoylated Ubc9的晶体结构表明，新创建的结合界面如何提供亲和力的增加，否则由E3连接酶提供。
Posttranslational modification with small ubiquitin-related modifier, SUMO, is a widespread mechanism for rapid and reversible changes in protein function. Considering the large number of known targets, the number of enzymes involved in modification seems surprisingly low: a single El, a single E2, and a few distinct E3 ligases. Here we show that autosumoylation of the mammalian E2-conjugating enzyme Ubc9 at Lys14 regulates target discrimination. While not altering its activity toward HDAC4, E2-25K, PML, or TDG, sumoylation of Ubc9 impairs its activity on RanGAP1 and strongly activates sumoylation of the transcriptional regulator Sp100. Enhancement depends on a SUMO-interacting motif (SIM) in Sp100 that creates an additional interface with the SUMO conjugated to the E2, a mechanism distinct from Ubc9 similar to SUMO thioester recruitment. The crystal structure of sumoylated Ubc9 demonstrates how the newly created binding interface can provide a gain in affinity otherwise provided by E3 ligases.