Food Science Graduate Group Department of Microbiology, University of California, Davis, California, USA.
Mol Microbiol. 2011 Oct;82(2):275-86. doi: 10.1111/j.1365-2958.2011.07829.x. Epub 2011 Sep 29.
Bifunctional sensor transmitter modules of two-component systems exert both positive and negative control on the receiver domain of the cognate response regulator. In negative control, the transmitter module accelerates the rate of phospho-receiver dephosphorylation. This transmitter phosphatase reaction serves the important physiological functions of resetting response regulator phosphorylation level and suppressing cross-talk. Although the biochemical reactions underlying positive control are reasonably well understood, the mechanism for transmitter phosphatase activity has been unknown. A recent hypothesis is that the transmitter phosphatase reaction is catalysed by a conserved Gln, Asn or Thr residue, via a hydrogen bond between the amide or hydroxyl group and the nucleophilic water molecule in acyl-phosphate hydrolysis. This hypothetical mechanism closely resembles the established mechanisms of auxiliary phosphatases such as CheZ and CheX, and may be widely conserved in two-component signal transduction. In addition to the proposed catalytic residues, transmitter phosphatase activity also requires the correct transmitter conformation and appropriate interactions with the receiver. Evidence suggests that the phosphatase-competent and autokinase-competent states are mutually exclusive, and the corresponding negative and positive activities are likely to be reciprocally regulated through dynamic control of transmitter conformations.
双组分系统的双功能传感器发射器模块对同源响应调节剂的受体结构域施加正、负控制。在负控制中，发射器模块加速磷酸化受体去磷酸化的速率。这种发射器磷酸酶反应具有重要的生理功能，可重置响应调节剂的磷酸化水平并抑制串扰。尽管正控制的生化反应已得到很好的理解，但发射器磷酸酶活性的机制尚不清楚。最近的一个假设是，通过酰胺或羟基与酰基磷酸水解中的亲核水分子之间的氢键，由保守的 Gln、Asn 或 Thr 残基催化发射器磷酸酶反应。这种假设的机制与辅助磷酸酶（如 CheZ 和 CheX）的既定机制非常相似，并且可能在双组分信号转导中广泛保守。除了提议的催化残基外，发射器磷酸酶活性还需要正确的发射器构象和与受体的适当相互作用。有证据表明，磷酸酶活性状态和自激酶活性状态是相互排斥的，并且相应的正、负活性可能通过发射器构象的动态控制相互调节。
