Transmembrane signaling in the sensor kinase DcuS of
            <i>Escherichia coli</i>
            : A long-range piston-type displacement of transmembrane helix 2

Monzel, Christian; Unden, Gottfried

doi:10.1073/pnas.1507217112

Cited by 28 publications

(79 citation statements)

References 41 publications

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“…After modulator addition, a slight increase in the level of Peg-Mal labeling was observed at position 559, which seems to mirror the effect at position 546. These results are qualitatively consistent with the model that the response to modulation implies a small, symmetrical movement of the TM helices toward the periplasm, in a manner similar to that observed in the sensor kinase DcuS, but with a smaller amplitude (34). However, additional movements of the TM helices cannot be ruled out with the current data.…”

Section: Resultssupporting

confidence: 91%

“…This argues against large displacement of the two helices relative to one another in response to modulation. Interestingly, similar results have been reported for the sensor kinases DcuS and EnvZ (34,35). Those authors have instead proposed a symmetrical piston movement of the TM helices to transduce the signal.…”

Section: Resultssupporting

confidence: 76%

“…Those authors have instead proposed a symmetrical piston movement of the TM helices to transduce the signal. To test this hypothesis with BvgS, we performed Cys accessibility experiments in B. pertussis in order to distinguish between residues outside and inside the hydrophobic portion of the lipid bilayer (34). Briefly, the bacteria were treated with N-ethylmaleimide (NEM) to modify the free Cys residues that are in a hydrated environment on either side of the membrane.…”

Section: Resultsmentioning

confidence: 99%

“…This signaling appears to involve a small symmetrical displacement of the TM helices of BvgS toward the periplasm. Piston motions of similar amplitudes are not unprecedented in sensory proteins; asymmetric and symmetric 1-to 2-Å piston motions have been reported for the chemoreceptors Tar and Tsr, as well as for the sensor kinases NarX and TorS, respectively (34,40,54,55).…”

Section: Mechanical Signal Transmission By Bvgs Linkermentioning

confidence: 97%

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Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS

et al. 2017

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The whooping cough agent, Bordetella pertussis, controls the expression of its large virulence regulon in a coordinated manner through the two-component system BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane segment, a cytoplasmic Per-Arnt-Sim (PAS) domain, a kinase module, and additional phosphorelay domains. BvgS shifts between kinase and phosphatase modes of activity in response to chemical modulators that modify the clamshell motions of the VFT domains. We have shown previously that this regulation involves a shift between distinct states of conformation and dynamics of the two-helix coiled-coil linker preceding the enzymatic module. In this work, we determined the mechanism of signal transduction across the membrane via a first linker, which connects the VFT and PAS domains of BvgS, using extensive cysteine cross-linking analyses and other approaches. Modulator perception by the periplasmic domains appears to trigger a small, symmetrical motion of the transmembrane segments toward the periplasm, causing rearrangements of the noncanonical cytoplasmic coiled coil that follows. As a consequence, the interface of the PAS domains is modified, which affects the second linker and eventually causes the shift of enzymatic activity. The major features of this first linker are well conserved among BvgS homologs, indicating that the mechanism of signal transduction unveiled here is likely to be generally relevant for this family of sensor kinases.IMPORTANCE Bordetella pertussis produces virulence factors coordinately regulated by the two-component system BvgAS. BvgS is a sensor kinase, and BvgA is a response regulator that activates gene transcription when phosphorylated by BvgS. Sensor kinases homologous to BvgS are also found in other pathogens. Our goal is to decipher the mechanisms of BvgS signaling, since these sensor kinases may represent new targets for antibacterial agents. Signal perception by the sensor domains of BvgS triggers small motions of the helical linker region underneath. The protein domain that follows this linker undergoes a large conformational change that amplifies the initial signal, causing a shift of activity from kinase to phosphatase. Because BvgS homologs harbor similar regions, these signaling mechanisms are likely to apply generally to that family of sensor kinases.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Mechanical Signal Transmission By Bvgs Linkermentioning

confidence: 97%

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Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS

et al. 2017

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“…Whereas these models are in most cases predicted from isolated domains, cysteine crosslinking in PhoQ (24) and water accessibility studies on DcuS (43) directly probe the TM segments. Bayesian modeling based on cross-linking data suggests a scissoring movement of TM helices for PhoQ, whereas water accessibility of both states of DcuS is in favor of a piston-type pull.…”

Section: Discussionmentioning

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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Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

Gushchin

Gordeliy

2017

BioEssays

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Allosteric and transmembrane (TM) signaling are among the major questions of structural biology. Here, we review and discuss signal transduction in four-helical TM bundles, focusing on histidine kinases and chemoreceptors found in two-component systems. Previously, piston, scissors, and helical rotation have been proposed as the mechanisms of TM signaling. We discuss theoretically possible conformational changes and examine the available experimental data, including the recent crystallographic structures of nitrate/nitrite sensor histidine kinase NarQ and phototaxis system NpSRII:NpHtrII. We show that TM helices can flex at multiple points and argue that the various conformational changes are not mutually exclusive, and often are observed concomitantly, throughout the TM domain or in its part. The piston and scissoring motions are the most prominent motions in the structures, but more research is needed for definitive conclusions.

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Transmembrane signaling in the sensor kinase DcuS of Escherichia coli : A long-range piston-type displacement of transmembrane helix 2

Cited by 28 publications

References 41 publications

Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS

Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS

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

Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

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