Structural basis of KdpD histidine kinase binding to the second messenger c-di-AMP

Dutta, Avijit; Batish, Mona; Parashar, Vijay

doi:10.1016/j.jbc.2021.100771

Cited by 16 publications

(6 citation statements)

References 95 publications

(177 reference statements)

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“…As a second messenger, c-di-AMP initiates signal transduction by binding to receptors that regulate downstream cellular processes. c-di-AMP receptors include enzymes such as the pyruvate carboxylase in L. monocytogenes and L. lactis (38,39), osmolyte transporters (28,(40)(41)(42)(43)(44)(45)(46), transcriptional regulators (20,21,47), and the KdpD sensor kinase of the KdpDE potassium-responsive two-component regulatory system (48,49). In addition, c-di-AMP-responding riboswitches controlling the expression of genes encoding K + uptake systems in B. subtilis and Bacillus thuringiensis have also been identified (19,50,51).…”

Section: Introductionmentioning

confidence: 99%

c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization by Clostridioides difficile

et al. 2022

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To colonize the host and cause disease, the human enteropathogen Clostridioides difficile must sense, respond, and adapt to the harsh environment of the gastrointestinal tract. We showed that the production and degradation of cyclic diadenosine monophosphate (c-di-AMP) were necessary during different phases of C. difficile growth, environmental adaptation, and infection. The production of this nucleotide second messenger was essential for growth because it controlled the uptake of potassium and also contributed to biofilm formation and cell wall homeostasis, whereas its degradation was required for osmotolerance and resistance to detergents and bile salts. The c-di-AMP binding transcription factor BusR repressed the expression of genes encoding the compatible solute transporter BusAA-AB. Compared with the parental strain, a mutant lacking BusR was more resistant to hyperosmotic and bile salt stresses, whereas a mutant lacking BusAA was more susceptible. A short exposure of C. difficile cells to bile salts decreased intracellular c-di-AMP concentrations, suggesting that changes in membrane properties induce alterations in the intracellular c-di-AMP concentration. A C. difficile strain that could not degrade c-di-AMP failed to persist in a mouse gut colonization model as long as the wild-type strain did. Thus, the production and degradation of c-di-AMP in C. difficile have pleiotropic effects, including the control of osmolyte uptake to confer osmotolerance and bile salt resistance, and its degradation is important for host colonization.

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Section: Introductionmentioning

confidence: 99%

c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization by Clostridioides difficile

et al. 2022

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“…In Staphylococcus aureus KdpD, the Usp domain was reported to bind c-di-AMP, a second messenger, which in general has been implicated in a wide range of osmotic and K + homeostasis regulation mechanisms 40 . Binding of c-di-AMP led to the downregulation of kdpFABC expression 41 , 42 . Consequently, we suspected that c-di-AMP binding to the Usp domain could be the signal for ASK stimulation in KdpD versions lacking K + sensing domains.…”

Section: Resultsmentioning

confidence: 98%

KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally

Silberberg,

Ketter,

Böhm

et al. 2024

Nat Commun

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Two-component systems, consisting of a histidine kinase and a response regulator, serve signal transduction in bacteria, often regulating transcription in response to environmental stimuli. Here, we identify a tandem serine histidine kinase function for KdpD, previously described as a histidine kinase of the KdpDE two-component system, which controls production of the potassium pump KdpFABC. We show that KdpD additionally mediates an inhibitory serine phosphorylation of KdpFABC at high potassium levels, using not its C-terminal histidine kinase domain but an N-terminal atypical serine kinase domain. Sequence analysis of KdpDs from different species highlights that some KdpDs are much shorter than others. We show that, while Escherichia coli KdpD’s atypical serine kinase domain responds directly to potassium levels, a shorter version from Deinococcus geothermalis is controlled by second messenger cyclic di-AMP. Our findings add to the growing functional diversity of sensor kinases while simultaneously expanding the framework for regulatory mechanisms in bacterial potassium homeostasis.

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“…In Staphylococcus aureus KdpD, the Usp domain was reported to bind c-di-AMP, a second messenger which in general has been implicated in a wide range of osmotic and K + homeostasis regulation mechanisms (Stülke and Krüger, 2020). Binding of c-di-AMP led to the downregulation of kdpFABC expression (Dutta et al, 2021; Moscoso et al, 2016). Consequently, we suspected that c-di-AMP binding to the Usp domain could be the signal for ASK stimulation in KdpD versions lacking K + sensing domains.…”

Section: Resultsmentioning

confidence: 99%

Sensory kinase KdpD is a tandem serine histidine kinase controlling K⁺pump KdpFABC on the translational and post-transcriptional level

Silberberg,

Ketter,

Böhm

et al. 2023

Preprint

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Two-component systems (TCSs), consisting of a histidine kinase (HK) and a response regulator, serve signal transduction in bacteria, often regulating transcription in response to environmental stimuli. Here, we identify a tandem serine histidine kinase function for KdpD, previously described as a HK of the TCS KdpDE, which controls production of the K+pump KdpFABC. We show that KdpD additionally mediates an inhibitory serine phosphorylation of KdpFABC at high K+levels, using not its C-terminal HK domain but an N-terminal atypical serine kinase (ASK) domain. Sequence analysis of KdpDs from different species highlights that some KdpDs comprise solely ASK and Usp domains. We show that, whileEscherichia coliKdpD’s ASK responds directly to K+levels, a shorter version fromDeinococcus geothermalisis controlled by second messenger cyclic di-AMP. Our findings add to the growing functional diversity of sensor kinases while simultaneously expanding the framework for regulatory mechanisms in bacterial K+homeostasis.

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Structural basis of KdpD histidine kinase binding to the second messenger c-di-AMP

Cited by 16 publications

References 95 publications

c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization by Clostridioides difficile

c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization by Clostridioides difficile

KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally

Sensory kinase KdpD is a tandem serine histidine kinase controlling K⁺pump KdpFABC on the translational and post-transcriptional level

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Structural basis of KdpD histidine kinase binding to the second messenger c-di-AMP

Cited by 16 publications

References 95 publications

c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization by Clostridioides difficile

c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization by Clostridioides difficile

KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally

Sensory kinase KdpD is a tandem serine histidine kinase controlling K+pump KdpFABC on the translational and post-transcriptional level

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Sensory kinase KdpD is a tandem serine histidine kinase controlling K⁺pump KdpFABC on the translational and post-transcriptional level