Structural insights into the signal transduction mechanism of the K+-sensing two-component system KdpDE

Sci Signal. 2020 Aug 4;13(643):eaaz2970. doi: 10.1126/scisignal.aaz2970.


Two-component systems (TCSs), which consist of a histidine kinase (HK) sensor and a response regulator (RR), are important for bacteria to quickly sense and respond to various environmental signals. HKs and RRs typically function as a cognate pair, interacting only with one another to transduce signaling. Precise signal transduction in a TCS depends on the specific interactions between the receiver domain (RD) of the RR and the dimerization and histidine phosphorylation domain (DHp) of the HK. Here, we determined the complex structure of KdpDE, a TCS consisting of the HK KdpD and the RR KdpE, which is responsible for K+ homeostasis. Both the RD and the DNA binding domain (DBD) of KdpE interacted with KdpD. Although the RD of KdpE and the DHp of KdpD contributed to binding specificity, the DBD mediated a distinct interaction with the catalytic ATP-binding (CA) domain of KdpD that was indispensable for KdpDE-mediated signal transduction. Moreover, the DBD-CA interface largely overlapped with that of the DBD-DNA complex, leading to competition between KdpD and its target promoter in a KdpE phosphorylation-dependent manner. In addition, the extended C-terminal tail of the CA domain was critical for stabilizing the interaction with KdpDE and for signal transduction. Together, these data provide a molecular basis for specific KdpD and KdpE interactions that play key roles in efficient signal transduction and transcriptional regulation by this TCS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Histidine Kinase / genetics
  • Histidine Kinase / metabolism
  • Models, Molecular
  • Mutation
  • Potassium / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Domains*
  • Protein Kinases / chemistry*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Signal Transduction*
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Escherichia coli Proteins
  • Trans-Activators
  • kdpE protein, E coli
  • KdpD protein, E coli
  • Protein Kinases
  • Histidine Kinase
  • Potassium