The YdiU Domain Modulates Bacterial Stress Signaling through Mn2+-Dependent UMPylation
The YdiU Domain Modulates Bacterial Stress Signaling through Mn2+-Dependent UMPylation
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YdiU 结构域通过 Mn2 依赖性 UMPylation 调节细菌应激信号
DOI：
10.1016/j.celrep.2020.108161
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发表时间：
2020-09-22
期刊：
影响因子：
8.8
通讯作者：
Li, Bingqing
中科院分区：
文献类型：
--
作者：
Yang, Yinlong;Yue, Yingying;Li, Bingqing
感知应激条件和调节细胞代谢以适应环境是细菌在多变的环境中生存的基本活动。在这里，我们描述了一种应激相关蛋白YdiU，并将YdiU描述为一种催化尿苷-5‘-单磷酸与蛋白质酪氨酸/组氨酸残基共价结合的酶，这种不寻常的修饰被定义为UMP化。Mn2+是YdiU介导的UMP化的重要辅助因子。UTP和Mn2+的结合将YdiU转化为易于聚集的状态，从而促进了伴侣的招募。伴侣蛋白的UMP化可以阻止它们与辅助因子或客户结合，从而损害它们的功能。与最近发现的YdiU作为AMPylator的作用相一致，我们进一步证明了YdiU的自我AMPY化锁定了它的伴侣-UMP化活性。基于APO-YdiU和YdiU-AMPNPP-Mn2+的晶体结构以及YdiU-UTP-Mn2+和YdiU-UTP-多肽的分子动力学模拟模型，提出了详细的反应机理。体内实验数据表明，YdiU通过UMP化有效地保护沙门氏菌免受应激所致的ATP耗竭。
Sensing stressful conditions and adjusting the cellular metabolism to adapt to the environment are essential activities for bacteria to survive in variable situations. Here, we describe a stress-related protein, YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine-5 '-monophosphate to a protein tyrosine/histidine residue, an unusual modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+ binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. A detailed mechanism is proposed based on the crystal structures of Apo-YdiU and YdiU-AMPNPP-Mn2+ and on molecular dynamics simulation models of YdiU-UTP-Mn2+ and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation.