Protein kinase sensors: an overview of new designs for visualizing kinase dynamics in single plant cells

Zhang, Li; Takahashi, Yohei; Schroeder, Julian I.

doi:10.1093/plphys/kiab277

Cited by 7 publications

(6 citation statements)

References 91 publications

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“…Bacterial transition-metal-sensing two-component systems are typically of the classical form and are composed of a membrane-bound dimeric HK that detects a metal ion concentration outside the cytoplasmic membrane while a cytosolic RR controls gene expression related to the particular transition metal that is sensed. In general, in the absence of transition metal ion binding, the sensor HK exists in a basal state with low kinase activity; , transition metal ion binding induces conformational and dynamical changes that activate the kinase activity of the sensor HK, leading to autophosphorylation at the conserved His residue. Once phosphorylated, a transfer of the phosphoryl group to the conserved Asp residue on the RR occurs, inducing separate conformational and dynamical changes that allow the RR to bind to DNA and to regulate gene expression .…”

Section: Transition-metal-sensing Two-component Systemsmentioning

confidence: 99%

Metal Messengers: Communication in the Bacterial World through Transition-Metal-Sensing Two-Component Systems

Paredes,

Iheacho,

Smith

2023

Biochemistry

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Bacteria survive in highly dynamic and complex environments due, in part, to the presence of systems that allow the rapid control of gene expression in the presence of changing environmental stimuli. The crosstalk between intra-and extracellular bacterial environments is often facilitated by two-component signal transduction systems that are typically composed of a transmembrane histidine kinase and a cytosolic response regulator. Sensor histidine kinases and response regulators work in tandem with their modular domains containing highly conserved structural features to control a diverse array of genes that respond to changing environments. Bacterial two-component systems are widespread and play crucial roles in many important processes, such as motility, virulence, chemotaxis, and even transition metal homeostasis. Transition metals are essential for normal prokaryotic physiological processes, and the presence of these metal ions may also influence pathogenic virulence if their levels are appropriately controlled. To do so, bacteria use transition-metal-sensing two-component systems that bind and respond to rapid fluctuations in extracytosolic concentrations of transition metals. This perspective summarizes the structural and metal-binding features of bacterial transition-metal-sensing two-component systems and places a special emphasis on understanding how these systems are used by pathogens to establish infection in host cells and how these systems may be targeted for future therapeutic developments.

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Section: Transition-metal-sensing Two-component Systemsmentioning

confidence: 99%

Metal Messengers: Communication in the Bacterial World through Transition-Metal-Sensing Two-Component Systems

Paredes,

Iheacho,

Smith

2023

Biochemistry

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“…A nonphosphorylated KTR locates within the nucleus via its NLS. Once there, phosphorylation of the NES allows KTR to exit the nucleus, which leads to the conversion of a phosphorylation event into a nucleocytoplasmic shuttling event [ 41 , 44 ].…”

Section: Framework For Engineering Genetically Encoded Plant-based Bi...mentioning

confidence: 99%

“…Protein phosphorylation plays key roles in signaling networks of cell differentiation, plant development, and stress responses [ 44 ]. Kinase translocation reporters (KTRs) have been used to enable spatiotemporal visualization of protein kinase activity in plant cells [ 91 ].…”

Section: Validated Biological Components For Different Types Of Plant...mentioning

confidence: 99%

Biological and Molecular Components for Genetically Engineering Biosensors in Plants

et al. 2022

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Plants adapt to their changing environments by sensing and responding to physical, biological, and chemical stimuli. Due to their sessile lifestyles, plants experience a vast array of external stimuli and selectively perceive and respond to specific signals. By repurposing the logic circuitry and biological and molecular components used by plants in nature, genetically encoded plant-based biosensors (GEPBs) have been developed by directing signal recognition mechanisms into carefully assembled outcomes that are easily detected. GEPBs allow for in vivo monitoring of biological processes in plants to facilitate basic studies of plant growth and development. GEPBs are also useful for environmental monitoring, plant abiotic and biotic stress management, and accelerating design-build-test-learn cycles of plant bioengineering. With the advent of synthetic biology, biological and molecular components derived from alternate natural organisms (e.g., microbes) and/or de novo parts have been used to build GEPBs. In this review, we summarize the framework for engineering different types of GEPBs. We then highlight representative validated biological components for building plant-based biosensors, along with various applications of plant-based biosensors in basic and applied plant science research. Finally, we discuss challenges and strategies for the identification and design of biological components for plant-based biosensors.

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“…Protein switches that are modulated by enzymatic inputs are promising tools to enable the investigation of PTM dynamics in cells 7,8 , the development of biocompatible nanodevices that sense PTM biomarkers for diagnosis or treatment of diseases, and the engineering of orthogonal signaling pathways to program the behavior of synthetic organisms 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the central function of PTMs as a molecular signaling (or “information-processing”) mechanism has been harnessed for the de novo design of protein switches that dynamically respond to phosphorylation by specific kinases and, in some cases, to dephosphorylation by phosphatases 3–6 . Protein switches that are modulated by enzymatic inputs are promising tools to enable the investigation of PTM dynamics in cells 7,8 , the development of biocompatible nanodevices that sense PTM biomarkers for diagnosis or treatment of diseases, and the engineering of orthogonal signaling pathways to program the behavior of synthetic organisms 9 .…”

Section: Introductionmentioning

confidence: 99%

Protein interaction kinetics delimit the performance of phosphorylation-driven protein switches

Winter,

Wairara,

Bennett

et al. 2023

Preprint

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Post-translational modifications (PTMs) such as phosphorylation and dephosphorylation can rapidly alter protein surface chemistry and structural conformation which can, in turn, switch protein-protein interactions (PPIs) within signaling networks. Recently,de novodesigned phosphorylation-responsive protein switches have been created that harness kinase- and phosphatase-mediated phosphorylation that modulate PPIs. PTM-driven protein switches could be useful for investigating PTM dynamics in living cells, developing biocompatible nanodevices, and engineering signaling pathways to program cell behavior. However, little is known about the physical and kinetic constraints of PTM-driven protein switches, which limits their practical application. In this study, we present a theoretical framework to evaluate two-component PTM-driven protein switches based on four performance metrics: effective concentration, dynamic range, response time, and reversibility. Our computational models reveal an intricate relationship between the binding kinetics, phosphorylation kinetics, and switch concentration that governs the sensitivity and reversibility of PTM-driven protein switches. Building upon the insights of our theoretical investigation, we built and evaluated two novel phosphorylation-driven protein switches consisting of phosphorylation-sensitive coiled coils as sensor domains fused to fluorescent proteins as actuator domains. By modulating the phosphorylation state of the switches with a specific protein kinase and phosphatase, we demonstrate fast, reversible transitions between easily differentiated “on” and “off” states. The response of the switches linearly correlated to the concentration of the kinase, demonstrating its potential as a biosensor for kinase measurements in real time. As intended, both switches responded to specific kinase activity with an increase in fluorescence signal and our model could be used to distinguish between two mechanisms of switch activation: dimerization or a structural rearrangement. In summary, the protein switch kinetics model presented here should be useful to guide the design of PTM-driven switches and tune their performance towards concrete applications.

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Protein kinase sensors: an overview of new designs for visualizing kinase dynamics in single plant cells

Cited by 7 publications

References 91 publications

Metal Messengers: Communication in the Bacterial World through Transition-Metal-Sensing Two-Component Systems

Metal Messengers: Communication in the Bacterial World through Transition-Metal-Sensing Two-Component Systems

Biological and Molecular Components for Genetically Engineering Biosensors in Plants

Protein interaction kinetics delimit the performance of phosphorylation-driven protein switches

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