An Unorthodox Sensory Adaptation Site in the Escherichia coli Serine Chemoreceptor

Han, Xuesheng; Parkinson, John S.

doi:10.1128/jb.01164-13

Cited by 27 publications

(37 citation statements)

References 38 publications

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“…1). In Tsr dimers E sites bias receptor output toward a kinase-OFF state, whereas Q residues mimic methylated E sites (Em) and shift output toward a kinase-ON state (1,9). In UU2567 (R − B − ), wild-type Tsr subunits encoded by plasmid pPA114 or plasmid pRR53 retain their [QEQEE] residue pattern and produce a serine response with a K 1/2 of ∼17 μM.…”

Section: Resultsmentioning

confidence: 99%

“…The HAMP-MH interplay poises the two bundles for stimulus responses: Attractants enhance HAMP stability to initiate a kinase-OFF output response; a subsequent methylation increase restores kinase-ON output during sensory adaptation. CheR preferentially acts on receptors in the OFF state; CheB preferentially acts on receptors in the ON state (1,9). AS1 (shown) and AS1′ are the N-terminal HAMP helices; AS2 and AS2′ (shown) are the C-terminal HAMP helices.…”

Section: Resultsmentioning

confidence: 99%

“…Those structural differences probably involve changes in substrate helix stability and changes in the packing interactions between helices of the methylation bundle (9,(16)(17)(18)(19).…”

mentioning

confidence: 99%

“…Adaptation site residues lie on solventexposed helix faces and share a consensus nine-residue motif at which CheR and CheB must bind for catalysis (13)(14)(15). Differences in higher-order structures of the methylation helix bundle presumably govern state-specific access to the substrate sites.Those structural differences probably involve changes in substrate helix stability and changes in the packing interactions between helices of the methylation bundle (9,(16)(17)(18)(19).The critical sensory adaptation roles of the CheR and CheB enzymes have been known for decades (20)(21)(22)(23)(24)(25). Here, we report that CheR has a second function that opposes the signaling consequences of its catalytic activity.…”

mentioning

confidence: 99%

“…The homodimeric serine chemoreceptor (Tsr) contains five adaptation sites per subunit (8,9), two of which are genetically encoded as glutaminyl (Q) residues, which mimic the signaling properties of Em sites (Fig. 1).…”

mentioning

confidence: 99%

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Paradoxical enhancement of chemoreceptor detection sensitivity by a sensory adaptation enzyme

Lai¹,

Han²,

Dahlquist³

et al. 2017

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

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A sensory adaptation system that tunes chemoreceptor sensitivity enables motile Escherichia coli cells to track chemical gradients with high sensitivity over a wide dynamic range. Sensory adaptation involves feedback control of covalent receptor modifications by two enzymes: CheR, a methyltransferase, and CheB, a methylesterase. This study describes a CheR function that opposes the signaling consequences of its catalytic activity. In the presence of CheR, a variety of mutant serine chemoreceptors displayed up to 40-fold enhanced detection sensitivity to chemoeffector stimuli. This response enhancement effect did not require the known catalytic activity of CheR, but did involve a binding interaction between CheR and receptor molecules. Response enhancement was maximal at low CheR:receptor stoichiometry and quantitative analyses argued against a reversible binding interaction that simply shifts the ON-OFF equilibrium of receptor signaling complexes. Rather, a short-lived CheR binding interaction appears to promote a long-lasting change in receptor molecules, either a covalent modification or conformation that enhances their response to attractant ligands.bacterial chemotaxis | receptor methyltransferase | dynamic-bundle model | signaling conformation | nonequilibrium mechanism M otile bacteria, despite their small size and simple cellular architecture, track chemical gradients in their living environments with extraordinary precision (see refs. 1 and 2 for reviews). They do so with only a handful of different proteins organized in a sensory signaling network that has stimulus integration, amplification, and memory capabilities. The extensively studied chemotaxis machinery of Escherichia coli has provided the molecular paradigm for transmembrane and intracellular signaling mechanisms in microbial chemosensory systems. This report describes a long-unrecognized activity of a central component of the E. coli chemotaxis machinery, suggesting that there are important new molecular lessons to learn from this structurally simple, yet functionally sophisticated, signaling system. E. coli senses attractant and repellent chemicals with transmembrane chemoreceptors known as methyl-accepting chemotaxis proteins (MCPs) (3). MCPs form networked arrays of signaling complexes, typically at the cell poles, that produce highly sensitive and cooperative responses to small chemoeffector concentration changes. The four MCPs of E. coli (Tsr, Tar, Tap, and Trg) have a common functional architecture comprising a periplasmic sensing domain and a cytoplasmic signaling domain (Fig. 1). An interposed HAMP domain communicates conformational changes between the sensing and signaling domains through an extended four-helix coiled-coil that contains sites for sensory adaptation adjustments of receptor signal output (4). The chemoreceptors modulate the activity of a histidine autokinase (CheA), which is stably coupled to receptors by a scaffolding protein (CheW). CheA donates its phosphoryl groups to CheY, a response regulator that in its phosphory...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Those structural differences probably involve changes in substrate helix stability and changes in the packing interactions between helices of the methylation bundle (9,(16)(17)(18)(19).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Paradoxical enhancement of chemoreceptor detection sensitivity by a sensory adaptation enzyme

Lai¹,

Han²,

Dahlquist³

et al. 2017

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

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The structural logic of dynamic signaling in the Escherichia coli serine chemoreceptor

Reyes,

Flack,

Parkinson

2024

Protein Science

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The experimental challenges posed by integral membrane proteins hinder molecular understanding of transmembrane signaling mechanisms. Here, we exploited protein crosslinking assays in living cells to follow conformational and dynamic stimulus signals in Tsr, the Escherichia coli serine chemoreceptor. Tsr mediates serine chemotaxis by integrating transmembrane serine‐binding inputs with adaptational modifications of a methylation helix bundle to regulate a signaling kinase at the cytoplasmic tip of the receptor molecule. We created cysteine replacements at Tsr residues adjacent to hydrophobic packing faces of the bundle helices and crosslinked them with a cell‐permeable, bifunctional thiol‐reagent. We identified an extensively crosslinked dynamic junction midway through the methylation helix bundle that seemed uniquely poised to respond to serine signals. We explored its role in mediating signaling shifts between different packing arrangements of the bundle helices by measuring crosslinking in receptor molecules with apposed pairs of cysteine reporters in each subunit and assessing their signaling behaviors with an in vivo kinase assay. In the absence of serine, the bundle helices evinced compact kinase‐ON packing arrangements; in the presence of serine, the dynamic junction destabilized adjacent bundle segments and shifted the bundle to an expanded, less stable kinase‐OFF helix‐packing arrangement. AlphaFold models of kinase‐active Tsr showed a prominent bulge and kink at the dynamic junction that might antagonize stable structure at the receptor tip. Serine stimuli might inhibit kinase activity by shifting the bundle to a less stably‐packed conformation that relaxes structural strain at the receptor tip, thereby allowing it to stabilize and freeze kinase activity.

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Regulation of the chemotaxis histidine kinase CheA: A structural perspective

Muok¹,

Briegel²,

Crane³

2020

Biochimica et Biophysica Acta (BBA) - Biomembranes

104

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Bacteria sense and respond to their environment through a highly conserved assembly of transmembrane chemoreceptors (MCPs), the histidine kinase (CheA), and the coupling protein CheW, hereafter termed "the chemosensory array". In recent years, great strides have been made in understanding the architecture of the underlying chemosensory arrays and how these assemblies engender sensitive and cooperative responses. Nonetheless, a central outstanding question surrounds how receptors modulate the activity of the chemotaxis kinase CheA, the enzymatic output of the sensory system. With a focus on recent advances, we summarize the current understanding of array structure and function to comment on the molecular mechanism by which CheA, receptors and CheW generate the high sensitivity, gain and dynamic range emblematic of bacterial chemotaxis. The complexity of the chemosensory arrays has motivated investigation with many different approaches. In particular, structural methods, genetics, cellular activity assays, nanodisc technology and cryo-electron tomography have provided advances that bridge length scales and connect molecular mechanism to cellular function. Given the high degree of component integration in the chemosensory arrays, we ultimately aim to understand how such networked molecular interactions generate a whole that is truly greater than the sum of its parts.

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An Unorthodox Sensory Adaptation Site in the Escherichia coli Serine Chemoreceptor

Cited by 27 publications

References 38 publications

Paradoxical enhancement of chemoreceptor detection sensitivity by a sensory adaptation enzyme

Paradoxical enhancement of chemoreceptor detection sensitivity by a sensory adaptation enzyme

The structural logic of dynamic signaling in the Escherichia coli serine chemoreceptor

Regulation of the chemotaxis histidine kinase CheA: A structural perspective

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