Negative control in two-component signal transduction by transmitter phosphatase activity

Food Science Graduate Group Department of Microbiology, University of California, Davis, California, USA.
Molecular Microbiology (Impact Factor: 4.42). 09/2011; 82(2):275-86. DOI: 10.1111/j.1365-2958.2011.07829.x
Source: PubMed


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.

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    • "In some sensor kinases it has been shown that within a conserved E/DxxT motif of the DHp domain, the Thr residue is critical for phosphatase activity (Huynh & Stewart, 2011; Willett & Kirby, 2012). FeuQ shares this conserved motif, but mutations to the conserved Thr did not give a phenotype consistent with eliminated phosphatase activity (data not shown). "
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    • "Detection of WalR~P amounts in pneumococcal cells 647 the strong dependence of the phosphatase activity on Mg 2+ ion (Zhu et al., 2000; Gutu et al., 2010; Huynh and Stewart, 2011). WalK with the T225A, S217A or R221K amino acid changes (Fig. S3C, D and H) showed similar low-level accumulation of WalR~P as wild-type WalK + in Mg 2+ buffer and were not ostensibly defective in phosphatase or other WalK activities. "
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    • "These pathways, a primary means of signal transduction in prokaryotes, typically involve a sensor histidine kinase that, upon receipt of an input stimulus, autophosphorylates and then transfers its phosphoryl group to a cognate response regulator, which in turn modulates gene expression (Stock et al., 2000). Most histidine kinases are bifunctional and can, in the absence of an input signal, stimulate the dephosphorylation of their cognate response regulators, effectively acting as phosphatases (Huynh and Stewart, 2011). "
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