ArticleScience advances2016
Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 86 citations in OpenAlex.
- Pharmacophore-guided identification and dynamic characterization of potential binders of the sporulation histidine kinase KinA in Bacillus subtilis.Archives of microbiology · 2026Article
- The oncogenic CCDC6-RET fusion protein is a dual ATP- and ADP-dependent kinase.Nature communications · 2026Article
- Dynamic Executors of Bacterial Signals: Functional Versatility and Regulatory Networks of c-di-GMP Effectors.Biomolecules · 2025Review
- Disrupting NtrC function reveals unexpected robustness in a central cell cycle regulatory network.mBio · 2025Article
- Insights Into the Conformational Dynamics of the Cytoplasmic Domain of Metal-Sensing Sensor Histidine Kinase ZraS.Proteins · 2025Article
- Article
- Cyclic Diguanylate in the Wild: Roles During Plant and Animal Colonization.Annual review of microbiology · 2024Review
- TheJournal of bacteriology · 2024Article
- A Model of the Full-Length Cytokinin Receptor: New Insights and Prospects.International journal of molecular sciences · 2023Article
- Sequestration of histidine kinases by non-cognate response regulators establishes a threshold level of stimulation for bacterial two-component signaling.Nature communications · 2023Article
- Evolution of cyclic di-GMP signalling on a short and long term time scale.Microbiology (Reading, England) · 2023Article
- Structural features discriminating hybrid histidine kinase Rec domains from response regulator homologs.Nature communications · 2023Article
- Mutant structure of metabolic switch protein in complex with monomeric c-di-GMP reveals a potential mechanism of protein-mediated ligand dimerization.Scientific reports · 2023Article
- Insights into the structure and function of the histidine kinase ComP from Bacillus amyloliquefaciens based on molecular modeling.Bioscience reports · 2022Article
- Dual Regulatory Role Exerted by Cyclic Dimeric GMP To Control FsnR-Mediated Bacterial Swimming.mBio · 2022Article
- Article
- Computational modeling of unphosphorylated CtrA:iScience · 2021Article
- Diversity in Sensing and Signaling of Bacterial Sensor Histidine Kinases.Biomolecules · 2021Review
- Molecular switch architecture determines response properties of signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di-guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.