CONTROL OF SIGMA B ACTIVITY IN B SUBTILIS

描述(改编自研究人员摘要)：枯草杆菌Sigma-B 蛋白质参与应激反应的转录激活 正规药。在没有环境压力的情况下，Sigma-B被保存在 具有抗Sigma的非活性复合体(RsbW)。未知的应力信号会导致 第二调节蛋白，RSBT，使其自身磷酸化并失活 抑制剂，RsbS。活性RSBT引导磷酸酶RsbU 使另一种调节剂RsbV去磷酸化。然后去磷酸化的RsbV可以 与RsbW结合，导致从Sigma-B释放，允许Sigma激活 作为转录因子。该系统被第二磷酸酶重置， RsbX，它使RsbS去磷酸化并重新激活，因此它可以再次 抑制RSBT。抑制RSBT会导致RsbV的磷酸化， 防止与RsbW交互，以便RsbW再次可用于 将sigma-B捕获在非活性络合物中。该提案试图确定如何 不同的压力可以与Sigma-B的调节器进行通信以控制 它的活动。RsbX缺失导致的高Sigma-B活性是有毒的 到细胞；这允许分离抑制子突变，并且 鉴定参与这一途径的基因。RSBT和RsbX是 被认为是环境信号最有可能的直接目标； 这将通过详细的突变分析进行测试。生化分析 将用于监测RBSS的体内磷酸化，这是建议的 是Sigma-B激活级联反应中的关键一步。相互作用的蛋白质 将通过生化分析和使用酵母来寻找具有RSB的蛋白质 双杂交系统。自从在致病基因中发现了Sigma-B同源物 细菌，分析控制应激反应可能会提供信息 关于对宿主的适应和传染性。

DESCRIPTION (adapted from investigator's abstract): The B. subtilis sigma-B protein is involved in activation of transcription of a stress response regulon. In the absence of environmental stress, sigma-B is held in an inactive complex with an anti-sigma (RsbW). Unknown stress signals cause a second regulatory protein, RsbT, to phosphorylate and inactivate its own inhibitor, RsbS. Active RsbT directs a phosphatase, RsbU, to dephosphorylate another regulator, RsbV. Dephosphorylated RsbV can then bind to RsbW, causing release from sigma-B, allowing the sigma to be active as a transcription factor. The system is reset by a second phosphatase, RsbX, which dephosphorylates and reactivates RsbS, so that it can again inhibit RsbT. Inhibition of RsbT results in phosphorylation of RsbV, preventing interaction with RsbW, so that RsbW is once again available to trap sigma-B in an inactive complex. The proposal seeks to determine how diverse stresses can communicate with the regulators of sigma-B to control its activity. High sigma-B activity, resulting from loss of RsbX, is toxic to the cell; this permits isolation of suppressor mutations, and identification of genes involved in this pathway. RsbT and RsbX are postulated to be the most likely direct targets of environmental signals; this will be tested by detailed mutational analysis. Biochemical analyses will be used to monitor in vivo phosphorylation of RbsS, which is proposed to be a key step in the sigma-B activation cascade. Proteins which interact with Rsb proteins will be sought by biochemical analyses and using the yeast dihybrid system. Since sigma-B homologs have been discovered in pathogenic bacteria, analysis of control of the stress response may provide information about adaptation to the host and infectivity.