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Structural and functional analysis of the Escherichia coli acid-sensing histidine kinase EvgS

Sen, Hrishiraj and Aggarwal, Nikhil and Ishionwu, Chibueze and Hussain, Nosheen and Parmar, Chandni and Jamshad, Mohammed and Bavro, Vassiliy N and Lund, Peter A (2017) 'Structural and functional analysis of the Escherichia coli acid-sensing histidine kinase EvgS.' Journal of Bacteriology, 199 (18). e00310-e00317. ISSN 0021-9193

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The EvgS/EvgA two-component system of Escherichia coli is activated in response to low pH and alkali metals and regulates many genes, including those for the glutamate-dependent acid resistance system and a number of efflux pumps. EvgS, the sensor kinase, is one of five unconventional histidine kinases (HKs) in E. coli and has a large periplasmic domain and a cytoplasmic PAS domain in addition to phospho-acceptor, HK and dimerization, internal receiver, and phosphotransfer domains. Mutations that constitutively activate the protein at pH 7 map to the PAS domain. Here, we built a homology model of the periplasmic region of EvgS, based on the structure of the equivalent region of the BvgS homologue, to guide mutagenesis of potential key residues in this region. We show that histidine 226 is required for induction and that it is structurally colocated with a proline residue (P522) at the top of the predicted transmembrane helix that is expected to play a key role in passing information to the cytoplasmic domains. We also show that the constitutive mutations in the PAS domain can be further activated by low external pH. Expression of the cytoplasmic part of the protein alone also gives constitutive activation, which is lost if the constitutive PAS mutations are present. These findings are consistent with a model in which EvgS senses both external and internal pH and is activated by a shift from a tight inactive to a weak active dimer, and we present an analysis of the purified cytoplasmic portion of EvgS that supports this.

Item Type: Article
Uncontrolled Keywords: Escherichia coli acid resistance histidine kinase periplasm signal transduction
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 08 Sep 2017 12:00
Last Modified: 13 May 2022 09:53

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