Plasticity of the PAS domain and a potential role for signal transduction in the histidine kinase DcuS

Etzkorn, Manuel; Kneuper, Holger; Dünnwald, Pia; Vijayan, Vinesh; Krämer, Jens; Griesinger, Christian; Becker, Stefan; Unden, Gottfried; Baldus, Marc

doi:10.1038/nsmb.1493

Cited by 82 publications

(117 citation statements)

References 57 publications

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“…Diverse experimental probes, ranging from limited proteolysis (30) to HDX-MS (31), have correlated changes in DHp structure and accessibility (caused by environmental change or mutation) to HK activity. Studies in other HK systems have found that altering interdomain interactions will impair signal transmission and even reverse its logic, as observed with the R175A mutation in EL346 (34,35). Combining this evidence with our findings, we propose that DHp movements elicit the release of inhibitory interactions analogous to those observed to sequester the CA domain in EL346's crystal structure (as evidenced by our limited trypsinolysis data), thus allowing the rearrangement of CA and DHp domains (Fig.…”

Section: Discussionsupporting

confidence: 82%

Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation

Rivera-Cancel

Tomchick

et al. 2014

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

100

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Although histidine kinases (HKs) are critical sensors of external stimuli in prokaryotes, the mechanisms by which their sensor domains control enzymatic activity remain unclear. Here, we report the full-length structure of a blue light-activated HK from Erythrobacter litoralis HTCC2594 (EL346) and the results of biochemical and biophysical studies that explain how it is activated by light. Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer. Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain. The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark. Upon light stimulation, interdomain interactions weaken to facilitate activation. Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation. We suggest parallels between EL346 and dimeric HKs, with sensor-induced movements in the DHp similarly remodeling the DHp/CA interface as part of activation.two-component system | cell signaling | histidine kinase | photosensory | regulation

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Section: Discussionsupporting

confidence: 82%

Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation

Rivera-Cancel

Tomchick

et al. 2014

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

100

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“…The reduction of CitA to the CitApc and the PASp domain constructs is justified as essential structural and binding properties are conserved in these constructs. This approach was previously used on the dicarboxylate receptor DcuS, another HK from the CitA family (26). However, we could not establish the mechanism for this HK because the ligand-free construct was not experimentally accessible (8,27).…”

Section: Resultsmentioning

confidence: 99%

“…First, G. thermodenitrificans CitA (Gt CitA, i.e., the complete HK) was characterized functionally. Citrate responsiveness and selectivity of Gt CitA was monitored by CitA-CitB receptor-dependent activity using a reporter gene assay as described previously for Escherichia coli DcuS (Ec DcuS) (26,28). Gt CitA was shown to be able to restore the CitA-CitB two-component system in a CitA-deficient E. coli strain in a citrate-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

Sensory domain contraction in histidine kinase CitA triggers transmembrane signaling in the membrane-bound sensor

Salvi

Schomburg

Giller

et al. 2017

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

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Bacteria use membrane-integral sensor histidine kinases (HK) to perceive stimuli and transduce signals from the environment to the cytosol. Information on how the signal is transmitted across the membrane by HKs is still scarce. Combining both liquid-and solid-state NMR, we demonstrate that structural rearrangements in the extracytoplasmic, citrate-sensing Per-Arnt-Sim (PAS) domain of HK CitA are identical for the isolated domain in solution and in a longer construct containing the membrane-embedded HK and lacking only the kinase core. We show that upon citrate binding, the PAS domain contracts, resulting in a shortening of the C-terminal β-strand. We demonstrate that this contraction of the PAS domain, which is well characterized for the isolated domain, is the signal transmitted to the transmembrane (TM) helices in a CitA construct in liposomes. Putting the extracytoplasmic PAS domain into context of the membrane-embedded CitA construct slows down citrate-binding kinetics by at least a factor of 60, confirming that TM helix motions are linked to the citrate-binding event. Our results are confirmation of a hallmark of the HK signal transduction mechanism with atomic resolution on a full-length construct lacking only the kinase core domain.transmembrane receptors | solid-state NMR spectroscopy | transmembrane signaling | integrated structural biology | histidine sensor kinase H istidine kinases (HKs) are key players in prokaryotic signaling and the primary means of processing extracellular stimuli (1-6). Due to their modular organization, HKs can relay a multitude of different input stimuli, including sensing of nutrients, light, physicochemical parameters (e.g., metal ions, ions gradient), temperature, oxygen, and molecules reporting cell density, to accomplish diverse responses. Over the last decade, various structures have been solved for the cytosolic kinase core and a number of signaling domains and more recently even for the complete cytoplasmic region (7-13), but the transmembrane (TM) signaling mechanism itself remains challenging to decipher. Structural information on individual stimulus-receiving domains therefore provides an important tool to identify TM signal transduction schemes.Because extracytoplasmic receiver domains are generally directly connected to TM helices, structural rearrangements within these motifs can be correlated with the TM-signaling mechanism. Different receiver domains have been characterized with and without their ligands and reveal structural differences between the two states that impose restraints on possible motions of the TM helices. Based on such structures, a symmetry-to-asymmetry switch has been postulated for KinB (14), TorT/TorS (15), and LuxPQ (16), implying a possible tilt of TM helices (17). For chemotaxis sensor Tar and for HK NarX a piston movement of the second TM helix has been postulated as a consequence of receiver domain motions (9,(18)(19)(20).Among receiver domains, PAS domains stand out by being able to process diverse input signals, which is reflected by...

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“…The importance of AЈ␣ is further illustrated by a deletion series; successive removal of residues from AЈ␣ yielded variants with ON, OFF, or INV phenotype (47). In the C 4 -dicarboxylate sensor DcuS from E. coli two ON mutations were identified in strand H␤ and in the loop between B␤ and C␣ (48). Last, for the widely studied PAS A domain of the B. subtilis sporulation kinase KinA certain mutations of residues within the ␤ sheet affect kinase activity (49); however, as these mutations were only studied in one signal state, their effect on regulation by signal is unknown.…”

Section: Discussionmentioning

confidence: 99%

Charting the Signal Trajectory in a Light-Oxygen-Voltage Photoreceptor by Random Mutagenesis and Covariance Analysis

Gleichmann

Diensthuber

Möglich

2013

Journal of Biological Chemistry

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Background: Modular receptors like the photoreceptor YF1 detect signals and process them into biological responses. Results: We identify numerous residues in the photosensor module of YF1 governing signal detection and processing. Conclusion: Spatial clustering of these residues delineates structurally contiguous regions in the photosensor crucially involved in signal transduction. Significance: The underlying mechanistic principles are widely shared in signal receptors.

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Plasticity of the PAS domain and a potential role for signal transduction in the histidine kinase DcuS

Cited by 82 publications

References 57 publications

Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation

Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation

Sensory domain contraction in histidine kinase CitA triggers transmembrane signaling in the membrane-bound sensor

Charting the Signal Trajectory in a Light-Oxygen-Voltage Photoreceptor by Random Mutagenesis and Covariance Analysis

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