A General Mechanism for the General Stress Response in Bacteria.
A General Mechanism for the General Stress Response in Bacteria.
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细菌一般应激反应的一般机制。
DOI：
10.1101/2024.02.16.580724
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Bradshaw,Niels
中科院分区：
文献类型：
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作者：
Baral,Rishika;Ho,Kristin;Ramasamy,PremK;Hopkins,JesseB;Watkins,MaxwellB;LaRussa,Salvatore;Caban-Penix,Suhaily;Calderone,LoganA;Bradshaw,Niels
细菌具有广泛保守的一般应激反应(GSR)，使它们能够在不利的环境条件下生存。然而，由于启动GSR的信号蛋白已经进化成对大量物种特有的信号做出反应，我们对它们是如何控制的缺乏普遍的理解。在这里，我们确定了PPM蛋白丝氨酸/苏氨酸磷酸酶家族的一个成员RsbU激活GSR INB的分子机制。枯草杆菌。已知RsbU的磷酸酶活性是通过与辅助蛋白RSBT相互作用而激活的，但RSBT是如何激活RsbU的还不清楚。在这里，我们报道了RSBT通过保守的变构开关元件结合RsbU的一个灵活的连接子来二聚化和激活它的磷酸酶结构域。已知同源连接物的构象柔性控制THE的活性。ColiGSR激活蛋白(RSSB)，它缺乏磷酸酶活性，功能是一种蛋白酶适配蛋白，这为跨细菌门的GSR激活提供了一个统一的模型。此外，正如我们现在所显示的，在活性二聚体状态下，RsBU连接子的交叉α-螺旋构象类似于预测的具有不同N-末端感觉结构域的旁系细菌磷酸酶，以及控制GGDEF二鸟苷环化酶和组氨酸激酶活性的连接子。我们认为，这种共享的调控机制为细菌识别不同的环境信号提供了一个可模块交换的工具包。
Bacteria have a widely conserved General Stress Response (GSR) that allows them to survive adverse environmental conditions. However, because the signaling proteins that initiate the GSR have evolved to respond to a vast range of species-specific signals, we lack a general understanding of how they are controlled. Here, we determined the molecular mechanism by which a member of the PPM family of protein serine/threonine phosphatases, RsbU, activates the GSR inB. subtilis. It was known that the phosphatase activity of RsbU is activated through interaction with a partner protein, RsbT, when it is released from a megadalton stress-sensing complex upon environmental stress, but how RsbT activates RsbU was not understood. Here we report that RsbT binds an otherwise flexible linker of RsbU to dimerize and activate its phosphatase domains through a conserved allosteric switch element. Conformational flexibility of the homologous linker was known to control activity of theE. coliGSR-activating protein (RssB), which lacks phosphatase activity and functions as a protease adapter protein, suggesting a unifying model for GSR activation across bacterial phyla. Furthermore, and as we now show, the crossing α-helical conformation of RsbU linkers in the active dimeric state is similar to that predicted for paralogous bacterial phosphatases with diverse N-terminal sensory domains, and to linkers known to control the activity of GGDEF diguanylate cyclases and histidine kinases. We propose that this shared regulatory mechanism provides a modularly exchangeable toolkit for bacteria to recognize diverse environmental signals.