Design and Signaling Mechanism of Light-Regulated Histidine Kinases

Möglich, Andreas; Ayers, Rebecca A.; Moffat, Keith

doi:10.1016/j.bpj.2008.12.2706

Cited by 74 publications

(179 citation statements)

References 49 publications

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“…6B) that forms the interface to the coaxial AЈ␣ and J␣ coiled-coils. Both the AЈ␣ and J␣ regions Nand C-terminal to the PAS domain core display helical signatures with numerous short-range sequential covarying pairs, in agreement with previous evidence for helical confirmation at both the sequence and structural levels (4,11,17,34). As our structural and functional data implicate the AЈ␣ and J␣ coiledcoils in signal transduction and modulation (see above and Ref.…”

Section: Random Mutagenesis Of the Light-oxygen-voltagesupporting

confidence: 91%

“…Mutational analysis supported this notion in that single amino acid exchanges in this region severely affected proper light regulation of the two-component system. We proposed the rotaryswitch model for signal transduction (11,17), which envisions that signals trigger conformational rearrangements of the sensor module that propagate as torque within coiled-coil linkers to the effector module where they modulate activity.…”

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confidence: 99%

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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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Section: Random Mutagenesis Of the Light-oxygen-voltagesupporting

confidence: 91%

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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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“…2A). The involvement of α-helices in mediating intramolecular signal transduction is not unique to bacteriophytochromes, and other researchers have used such helices for heterologous domain replacements (43)(44)(45)(46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Engineering adenylate cyclases regulated by near-infrared window light

Ryu

Kang

Nelson

et al. 2014

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

108

114

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Bacteriophytochromes sense light in the near-infrared window, the spectral region where absorption by mammalian tissues is minimal, and their chromophore, biliverdin IXα, is naturally present in animal cells. These properties make bacteriophytochromes particularly attractive for optogenetic applications. However, the lack of understanding of how light-induced conformational changes control output activities has hindered engineering of bacteriophytochromebased optogenetic tools. Many bacteriophytochromes function as homodimeric enzymes, in which light-induced conformational changes are transferred via α-helical linkers to the rigid output domains. We hypothesized that heterologous output domains requiring homodimerization can be fused to the photosensory modules of bacteriophytochromes to generate light-activated fusions. Here, we tested this hypothesis by engineering adenylate cyclases regulated by light in the near-infrared spectral window using the photosensory module of the Rhodobacter sphaeroides bacteriophytochrome BphG1 and the adenylate cyclase domain from Nostoc sp. CyaB1. We engineered several light-activated fusion proteins that differed from each other by approximately one or two α-helical turns, suggesting that positioning of the output domains in the same phase of the helix is important for light-dependent activity. Extensive mutagenesis of one of these fusions resulted in an adenylate cyclase with a sixfold photodynamic range. Additional mutagenesis produced an enzyme with a more stable photoactivated state. When expressed in cholinergic neurons in Caenorhabditis elegans, the engineered adenylate cyclase affected worm behavior in a light-dependent manner. The insights derived from this study can be applied to the engineering of other homodimeric bacteriophytochromes, which will further expand the optogenetic toolset.phytochrome | protein engineering | adenylyl cyclase | cAMP | locomotion

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“…The mechanism proposed for EL346 supports these overarching principles governing HK regulation, regardless of oligomeric state and cellular localization: (i) Changes in the sensor are propagated via movements of the DHp (or DHpL) helices and (ii) these movements result in structural remodeling of the interface with the CA, leading to changes in HK activity. Previous studies have shown that signaling relies on DHp movements (31) and that sensors often use helical connectors to affect DHp structure, dynamics, and flexibility at a distance (22,30,32,33). 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.…”

Section: Discussionmentioning

confidence: 99%

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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Design and Signaling Mechanism of Light-Regulated Histidine Kinases

Cited by 74 publications

References 49 publications

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

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

Engineering adenylate cyclases regulated by near-infrared window light

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

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