Cell Fate Regulation Governed by a Repurposed Bacterial Histidine Kinase

Childers, W. Seth; Xu, Qingping; Mann, Thomas H.; Mathews, I.I.; Blair, Jimmy A.; Deacon, Ashley M.; Shapiro, Lucy

doi:10.1371/journal.pbio.1001979

Cited by 67 publications

(85 citation statements)

References 66 publications

(115 reference statements)

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“…S5(A)] indicate that these interaction sites are flexible. This is consistent with the known behavior of other histidine kinases . Interestingly, contact with the RR protein also appears to stabilize an additional segment of the Af GcHK kinase domain, which includes helix H12, loop L16 and part of β‐strand B4.…”

Section: Discussionsupporting

confidence: 83%

Structural characterization of the heme‐based oxygen sensor, AfGcHK, its interactions with the cognate response regulator, and their combined mechanism of action in a bacterial two‐component signaling system

et al. 2016

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The oxygen sensor histidine kinase AfGcHK from the bacterium Anaeromyxobacter sp. Fw 109-5 forms a two-component signal transduction system together with its cognate response regulator (RR). The binding of oxygen to the heme iron of its N-terminal sensor domain causes the C-terminal kinase domain of AfGcHK to autophosphorylate at His183 and then transfer this phosphate to Asp52 or Asp169 of the RR protein. Analytical ultracentrifugation revealed that AfGcHK and the RR protein form a complex with 2:1 stoichiometry. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) suggested that the most flexible part of the whole AfGcHK protein is a loop that connects the two domains and that the heme distal side of AfGcHK, which is responsible for oxygen binding, is the only flexible part of the sensor domain. HDX-MS studies on the AfGcHK:RR complex also showed that the N-side of the H9 helix in the dimerization domain of the AfGcHK kinase domain interacts with the helix H1 and the β-strand B2 area of the RR protein's Rec1 domain, and that the C-side of the H8 helix region in the dimerization domain of the AfGcHK protein interacts mostly with the helix H5 and β-strand B6 area of the Rec1 domain. The Rec1 domain containing the phosphorylable Asp52 of the RR protein probably has a significantly higher affinity for AfGcHK than the Rec2 domain. We speculate that phosphorylation at Asp52 changes the overall structure of RR such that the Rec2 area containing the second phosphorylation site (Asp169) can also interact with AfGcHK. Proteins 2016; 84:1375-1389. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 83%

Structural characterization of the heme‐based oxygen sensor, AfGcHK, its interactions with the cognate response regulator, and their combined mechanism of action in a bacterial two‐component signaling system

et al. 2016

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“…In Caulobacter cells protein complexes of different composition are assembled at opposite cell poles where they control cell-type-specific functions, including signaling protein-mediated differential expression of the genome after cell compartmentalization and MipZ-directed positioning of the divisome (12,13,15,(28)(29)(30)(31). During the swarmer to stalked cell transition, the protein complex of the formerly flagellated pole is replaced by the proteins required at a stalked pole protein complex.…”

Section: Spmx Is Synthesized In the Swarmer Cell For Immediate Localimentioning

confidence: 99%

“…The expression of cell cycle-controlled mRNAs largely correlates with the times they are required for the functional modules that implement progression of the cell cycle (8). The transcriptional activity of most of the Caulobacter cell cycle-regulated promoters is controlled by a genetic circuit comprised of four transcriptional master regulators, a DNA methyltransferase (2), and a dynamic set of polar-localized phospho-signaling proteins that control asymmetric cell division (12)(13)(14)(15). Because regulation of translation has an immediate impact on protein production, a major cellular energy drain, tight regulation of translation is essential for rapid cell adaptation to changing circumstances.…”

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confidence: 99%

Dynamic translation regulation in Caulobacter cell cycle control

Schrader

Childers

et al. 2016

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

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Progression of the Caulobacter cell cycle requires temporal and spatial control of gene expression, culminating in an asymmetric cell division yielding distinct daughter cells. To explore the contribution of translational control, RNA-seq and ribosome profiling were used to assay global transcription and translation levels of individual genes at six times over the cell cycle. Translational efficiency (TE) was used as a metric for the relative rate of protein production from each mRNA. TE profiles with similar cell cycle patterns were found across multiple clusters of genes, including those in operons or in subsets of operons. Collections of genes associated with central cell cycle functional modules (e.g., biosynthesis of stalk, flagellum, or chemotaxis machinery) have consistent but different TE temporal patterns, independent of their operon organization. Differential translation of operon-encoded genes facilitates precise cell cycle-timing for the dynamic assembly of multiprotein complexes, such as the flagellum and the stalk and the correct positioning of regulatory proteins to specific cell poles. The cell cycleregulatory pathways that produce specific temporal TE patterns are separate from-but highly coordinated with-the transcriptional cell cycle circuitry, suggesting that the scheduling of translational regulation is organized by the same cyclical regulatory circuit that directs the transcriptional control of the Caulobacter cell cycle.T he Caulobacter crescentus cell cycle produces two daughter cell types at each cell division: a nonreplicative motile swarmer cell, and a replication-competent sessile stalked cell. At the time of the asymmetric cell division, each daughter cell activates a different genetic program. Caulobacter has a cyclical genetic circuit that controls the varying temporal and spatial expression of multiple functional modules (Fig. 1) that implement biogenesis of polar organelles, replication and segregation of the chromosome, and cytokinesis (1-4). The circular 4-Mb genome has 3,885 ORFs and 199 noncoding RNAs (5, 6). mRNA profiling by microarrays or RNA-seq (7-10) and global promoter activity profiles from 5′ Global RACE experiments (11) have shown that several hundred Caulobacter mRNAs have significant temporal transcriptional variation over the cell cycle. The expression of cell cycle-controlled mRNAs largely correlates with the times they are required for the functional modules that implement progression of the cell cycle (8). The transcriptional activity of most of the Caulobacter cell cycle-regulated promoters is controlled by a genetic circuit comprised of four transcriptional master regulators, a DNA methyltransferase (2), and a dynamic set of polar-localized phospho-signaling proteins that control asymmetric cell division (12-15). Because regulation of translation has an immediate impact on protein production, a major cellular energy drain, tight regulation of translation is essential for rapid cell adaptation to changing circumstances. In eukaryotic cells translational contr...

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“…[1,3,13,14] Unlike many modular domainsc onnected by flexible linkers, histidine kinases appear to rely on rigidh elicall inkerst hat transmiti nformation between domains. [6,[16][17][18] Modeling based on aminoa cid insertion experiments now suggest that the relative position of these helices in the VirA dimer control kinase activity through combined piston and twisting motions. [1,9,19] Additional experimentsh ave further confirmed that the positioning of the anchoring TM2 trans-membrane helix is critical for sugar input into the Ldomain.…”

Section: Introductionmentioning

confidence: 99%

A Rhizobium radiobacter Histidine Kinase Can Employ Both Boolean AND and OR Logic Gates to Initiate Pathogenesis

et al. 2015

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The molecular logic gates that regulate gene circuits are necessarily intricate and highly regulated, particularly in the critical commitments necessary for pathogenesis. We now report simple AND and OR logic gates to be accessible within a single protein receptor. Pathogenesis by the bacterium Rhizobium radiobacter is mediated by a single histidine kinase, VirA, which processes multiple small molecule host signals (phenol and sugar). Mutagenesis analyses converged on a single signal integration node, and finer functional analyses revealed that a single residue could switch VirA from a functional AND logic gate to an OR gate where each of two signals activate independently. Host range preferences among natural strains of R. radiobacter correlate with these gate logic strategies. Although the precise mechanism for the signal integration node requires further analyses, long-range signal transmission through this histidine kinase can now be exploited for synthetic signaling circuits.

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Cell Fate Regulation Governed by a Repurposed Bacterial Histidine Kinase

Cited by 67 publications

References 66 publications

Structural characterization of the heme‐based oxygen sensor, AfGcHK, its interactions with the cognate response regulator, and their combined mechanism of action in a bacterial two‐component signaling system

Structural characterization of the heme‐based oxygen sensor, AfGcHK, its interactions with the cognate response regulator, and their combined mechanism of action in a bacterial two‐component signaling system

Dynamic translation regulation in Caulobacter cell cycle control

A Rhizobium radiobacter Histidine Kinase Can Employ Both Boolean AND and OR Logic Gates to Initiate Pathogenesis

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