Hybrid histidine kinase activation by cyclic di-GMP–mediated domain liberation

Dubey, Badri N.; Agustoni, Elia; Böhm, Raphael; Kaczmarczyk, Andreas; Mangia, Francesca; Arx, C. von; Jenal, Urs; Hiller, Sebastian; Plaza-Menacho, Iván; Schirmer, Tilman

doi:10.1073/pnas.1911427117

Cited by 34 publications

(39 citation statements)

References 37 publications

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“…We hypothesize that binding of c-di-GMP to REC1 interferes with this tethering, thereby liberating REC2 and facilitating the productive interaction between CA and DHp for autophosphorylation and eventually for phosphotransfer between DHp and REC2. This model is strongly supported by an accompanying structural analysis of ShkA 22 .…”

Section: Discussionmentioning

confidence: 54%

Precise timing of transcription by c-di-GMP coordinates cell cycle and morphogenesis in Caulobacter

et al. 2020

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Bacteria adapt their growth rate to their metabolic status and environmental conditions by modulating the length of their G1 period. Here we demonstrate that a gradual increase in the concentration of the second messenger c-di-GMP determines precise gene expression during G1/S transition in Caulobacter crescentus. We show that c-di-GMP stimulates the kinase ShkA by binding to its central pseudo-receiver domain, activates the TacA transcription factor, and initiates a G1/S-specific transcription program leading to cell morphogenesis and S-phase entry. Activation of the ShkA-dependent genetic program causes c-di-GMP to reach peak levels, which triggers S-phase entry and promotes proteolysis of ShkA and TacA. Thus, a gradual increase of c-di-GMP results in precise control of ShkA-TacA activity, enabling G1/Sspecific gene expression that coordinates cell cycle and morphogenesis.

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Section: Discussionmentioning

confidence: 54%

Precise timing of transcription by c-di-GMP coordinates cell cycle and morphogenesis in Caulobacter

et al. 2020

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“…We 329 hypothesize that binding of c-di-GMP to REC1 interferes with this tethering, thereby 330 liberating REC2 and facilitating the productive interaction between CA and DHp for 331 autophosphorylation and eventually for phosphotransfer between DHp and REC2. This 332 model is strongly supported by an accompanying structural analysis of ShkA 22 .…”

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confidence: 71%

Precise transcription timing by a second-messenger drives a bacterial G1/S cell cycle transition

Kaczmarczyk

Hempel

Arx

et al. 2019

Preprint

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29Bacteria adapt their growth rate to their metabolic status and environmental 30 conditions by modulating the length of their quiescent G1 period. But the molecular 31 mechanisms controlling G1 length and exit from G1 are poorly understood. Here we 32 identify a key role for the second messenger c-di-GMP, and demonstrate that a gradual 33 increase in c-di-GMP concentration determines precise gene expression during G1/S in 34 Caulobacter crescentus. We show that c-di-GMP strongly stimulates the kinase ShkA, 35activates the TacA transcription factor, and initiates a G1/S-specific transcription 36 program leading to cell morphogenesis and S-phase entry. C-di-GMP activates ShkA by 37 binding to its central pseudo-receiver domain uncovering this wide-spread domain as a 38 novel signal input module of bacterial kinases. Activation of the ShkA-dependent 39 genetic program also causes c-di-GMP to reach peak levels, which triggers S-phase 40 entry and, in parallel, promotes proteolysis of ShkA and TacA. Thus, a gradual 41 increase of c-di-GMP results in a precisely tuned ShkA-TacA activity window enabling 42 G1/S specific gene expression before cells commit to replication initiation. By defining 43 a regulatory mechanism for G1/S control, this study contributes to understanding 44 bacterial growth control at the molecular level. cell division (D or G2) 1 . Since chromosome replication and cell division (C and D 49 periods) remain constant over a wide range of growth rates 2,3 , the step committing 50 cells to initiate chromosome replication largely determines bacterial proliferation rates. 51Bacteria like Escherichia coli or Bacillus subtilis can increase their growth rate by 52 bypassing the B period and by initiating replication multiple times per division cycle 2 . 53In contrast, Caulobacter crescentus strictly separates its cell cycle stages. An 54 asymmetric division generates a sessile stalked (ST) cell, which directly re-enters S-55 phase, and a motile swarmer (SW) cell that remains in G1 for a variable time 56 depending on nutrient availability 4,5 . Coincident with G1/S transition, motile SW cells 57 undergo morphogenesis to gain sessility ( Fig. 1a). But what determines the length of 58 G1 in this organism has remained unclear. 59In C. crescentus, replication initiation is regulated by the cell cycle kinase CckA. 60CckA is a bifunctional enzyme that acts as a kinase for the replication initiation 61 inhibitor CtrA in G1, but switches to being a phosphatase in S phase, resulting in the 62 inactivation of CtrA and clearance of the replication block 6 (Fig. 1a). The CckA switch 63 is governed by two response regulators, DivK and PleD. While DivK controls CckA 64 activity through protein-protein interactions 7-9 , PleD is a diguanylate cyclase, which is 65 responsible for the characteristic oscillation of c-di-GMP during the cell cycle 10 . The 66 concentration of c-di-GMP, below the detection limit in G1, increases during G1/S to 67 reach peak levels at the onset of S-phase 11 where it allosterically stimulates Cc...

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“…Among them, we found the sensor kinase PleC that functions upstream and activates the diguanylate cyclase PleD over phosphorylation. The hybrid kinase ShkA comprises a downstream effector protein of PleD, which binds c-di-GMP and phosphorylates the TacA transcription factor responsible for the initiation of the stalked cellspecific transcription program (27,28). The flagellum assembly ATPase FlbE/FliH together with FliI and FliJ form the soluble component of the flagellar export apparatus, which, in Pseudomonas, has also been identified as a c-di-GMP effector complex (29).…”

Section: Components Of the C-di-gmp Signaling Network Are Conditionallymentioning

confidence: 99%

The type IV pilin PilA couples surface attachment and cell-cycle initiation in Caulobacter crescentus

Medico

Cerletti

Schächle

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Understanding how bacteria colonize surfaces and regulate cell-cycle progression in response to cellular adhesion is of fundamental importance. Here, we use transposon sequencing in conjunction with fluorescence resonance energy transfer (FRET) microscopy to uncover the molecular mechanism for how surface sensing drives cell-cycle initiation in Caulobacter crescentus. We identify the type IV pilin protein PilA as the primary signaling input that couples surface contact to cell-cycle initiation via the second messenger cyclic di-GMP (c-di-GMP). Upon retraction of pili filaments, the monomeric pilin reservoir in the inner membrane is sensed by the 17-amino acid transmembrane helix of PilA to activate the PleC-PleD two-component signaling system, increase cellular c-di-GMP levels, and signal the onset of the cell cycle. We termed the PilA signaling sequence CIP for “cell-cycle initiating pilin” peptide. Addition of the chemically synthesized CIP peptide initiates cell-cycle progression and simultaneously inhibits surface attachment. The broad conservation of the type IV pili and their importance in pathogens for host colonization suggests that CIP peptide mimetics offer strategies to inhibit surface sensing, prevent biofilm formation and control persistent infections.

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Hybrid histidine kinase activation by cyclic di-GMP–mediated domain liberation

Cited by 34 publications

References 37 publications

Precise timing of transcription by c-di-GMP coordinates cell cycle and morphogenesis in Caulobacter

Precise timing of transcription by c-di-GMP coordinates cell cycle and morphogenesis in Caulobacter

Precise transcription timing by a second-messenger drives a bacterial G1/S cell cycle transition

The type IV pilin PilA couples surface attachment and cell-cycle initiation in Caulobacter crescentus

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