Degradation of the membrane-localized virulence activator TcpP by the YaeL protease in Vibrio cholerae.
Degradation of the membrane-localized virulence activator TcpP by the YaeL protease in Vibrio cholerae.
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DOI：
10.1073/pnas.0505818102
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发表时间：
2005-11
影响因子：
11.1
通讯作者：
Jyl S Matson;V. DiRita
中科院分区：
文献类型：
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作者：
Jyl S Matson;V. DiRita
抑制转录因子活性的一种常见机制是它们被隔离在膜上，直到需要时，它们才通过蛋白质水解从膜上释放出来。与这种抑制机制相反的是霍乱弧菌的毒力调节因子，ToxR和TcpP蛋白，它们定位于细胞的内膜，在那里它们结合启动子DNA并激活基因表达。TcpP在缺乏另一种蛋白质TcpH的情况下被迅速降解。我们使用遗传筛选来确定TcpP稳定性的调节因子，并确定了YaeL膜定位的锌金属蛋白酶在TcpH缺失时负责降解TcpP。在大肠杆菌中，DegS和YaeL协同降解RseA， RseA是一种将sigma(E)隔离在内膜上的抗sigma因子，从而抑制sigma(E)的活性。当yaeL在霍乱弧菌tcpH突变体中被破坏时，我们观察到低分子量TcpP物种的积累。这一观察结果与TcpP在没有YaeL的情况下部分降级是一致的。缺乏DegS和YaeL的突变体继续积累TcpP降解产物，表明在降解TcpP时，DegS以外的蛋白酶先于YaeL发挥作用。在不利于毒力基因激活的条件下，依赖于yael的降解途径在TcpH（+）细胞中是活跃的。这项工作扩大了对细菌细胞中yael依赖性加工的了解，并揭示了霍乱弧菌中一个意想不到的毒力基因调控层。
A common mechanism inhibiting the activity of transcription factors is their sequestration to the membrane until they are needed, at which point they are released from the membrane by proteolysis. Acting in contrast to this inhibition mechanism are virulence regulators of Vibrio cholerae, the ToxR and TcpP proteins, which are localized to the inner membrane of the cell, where they bind promoter DNA and activate gene expression. TcpP is rapidly degraded in the absence of another protein, TcpH. We used a genetic screen to identify regulators of TcpP stability and identified the YaeL membrane-localized zinc metalloprotease as responsible for degrading TcpP in the absence of TcpH. In Escherichia coli, DegS and YaeL cooperate to degrade RseA, an antisigma factor that sequesters sigma(E) to the inner membrane, thereby inhibiting the activity of sigma(E). When yaeL was disrupted in a V. cholerae tcpH mutant, we observed accumulation of a lower molecular weight species of TcpP. This observation is consistent with TcpP being partially degraded in the absence of YaeL. A mutant lacking both DegS and YaeL continued to accumulate the TcpP degradation product, indicating that protease other than DegS is acting before YaeL in degrading TcpP. The YaeL-dependent degradation pathway is active in TcpH(+) cells under conditions that are not favorable for virulence gene activation. This work expands the knowledge of YaeL-dependent processing in the bacterial cell and reveals an unexpected layer of virulence gene regulation in V. cholerae.