3bqa
From Proteopedia
Crystal Structure of an E.coli PhoQ Sensor Domain Mutant
Structural highlights
Function[PHOQ_ECOLI] Member of the two-component regulatory system PhoP/PhoQ involved in adaptation to low Mg(2+) environments and the control of acid resistance genes. In low periplasmic Mg(2+), PhoQ functions as a membrane-associated protein kinase that undergoes autophosphorylation and subsequently transfers the phosphate to PhoP, resulting in the expression of PhoP-activated genes (PAG) and repression of PhoP-repressed genes (PRG). In high periplasmic Mg(2+), acts as a protein phosphatase that dephosphorylates phospho-PhoP, resulting in the repression of PAG and may lead to expression of some PRG (By similarity). PhoP-regulated transcription is redox-sensitive, being activated when the periplasm becomes more reducing (deletion of dsbA/dsbB, or treatment with dithiothreitol). MgrB acts between DsbA/DsbB and PhoP/PhoQ in this pathway; the 2 periplasmic Cys residues of MgrB are required for its action on PhoQ, which then acts on PhoP. Mediates magnesium influx to the cytosol by activation of mgtA. Promotes expression of the two-component regulatory system rstA/rstB and transcription of the hemL, mgrB, nagA, slyB, vboR and yrbL genes.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe PhoP-PhoQ two-component system is a well studied bacterial signaling system that regulates virulence and stress response. Catalytic activity of the histidine kinase sensor protein PhoQ is activated by low extracellular concentrations of divalent cations such as Mg2+, and subsequently the response regulator PhoP is activated in turn through a classic phosphotransfer pathway that is typical in such systems. The PhoQ sensor domains of enteric bacteria contain an acidic cluster of residues (EDDDDAE) that has been implicated in direct binding to divalent cations. We have determined crystal structures of the wild-type Escherichia coli PhoQ periplasmic sensor domain and of a mutant variant in which the acidic cluster was neutralized to conservative uncharged residues (QNNNNAQ). The PhoQ domain structure is similar to that of DcuS and CitA sensor domains, and this PhoQ-DcuS-CitA (PDC) sensor fold is seen to be distinct from the superficially similar PAS domain fold. Analysis of the wild-type structure reveals a dimer that allows for the formation of a salt bridge across the dimer interface between Arg-50' and Asp-179 and with nickel ions bound to aspartate residues in the acidic cluster. The physiological importance of the salt bridge to in vivo PhoQ function has been confirmed by mutagenesis. The mutant structure has an alternative, non-physiological dimeric association. Crystal structure of a functional dimer of the PhoQ sensor domain.,Cheung J, Bingman CA, Reyngold M, Hendrickson WA, Waldburger CD J Biol Chem. 2008 May 16;283(20):13762-70. Epub 2008 Mar 18. PMID:18348979[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Bacillus coli migula 1895 | Histidine kinase | Cheung, J | Hendrickson, W A | Waldburger, C D | Atp-binding | Histidine kinase sensor domain | Inner membrane | Magnesium | Membrane | Metal-binding | Nucleotide-binding | Phosphoprotein | Signaling protein | Transferase | Transmembrane | Two-component regulatory system
