Routes of phosphoryl group transfer during signal transmission and signal decay in the dimeric sensor histidine kinase ArcB

ABSTRACT The Arc two-component system, comprising a tripartite sensor kinase (ArcB) and a response regulator (ArcA), modulates the expression of numerous genes involved in respiratory functions. In this study, the steps of phosphoryl group transfer from phosphorylated ArcB to ArcA were examined in vivo by using single copies of wild-type and mutantarcB alleles. The results indicate that the signal transmission occurs solely by His-Asp-His-Asp phosphorelay.

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The Neurospora crassa DCC-1 Protein, a Putative Histidine Kinase, Is Required for Normal Sexual and Asexual Development and Carotenogenesis

Eukaryotic Cell ◽

10.1128/ec.05223-11 ◽

2011 ◽

Vol 10 (12) ◽

pp. 1733-1739 ◽

Cited By ~ 11

Author(s):

Carlos Barba-Ostria ◽

Fernando Lledías ◽

Dimitris Georgellis

Keyword(s):

Neurospora Crassa ◽

Histidine Kinase ◽

Response Regulator ◽

Protein A ◽

Phosphoryl Group ◽

Mutant Form ◽

Slime Molds ◽

Content Type ◽

Group Transfer ◽

Environmental Responses

ABSTRACT Two-component signaling pathways based on phosphoryl group transfer between histidine kinase and response regulator proteins regulate environmental responses in bacteria, archaea, plants, slime molds, and fungi. Here we characterize a mutant form of DCC-1, a putative histidine kinase encoded by the NCU00939 gene of the filamentous fungus Neurospora crassa . We show that this protein participates in the regulation of processes such as conidiation, perithecial development, and, to a certain degree, carotenogenesis. Furthermore, DCC-1 is suggested to exert its effect by promoting cyclic AMP production, thereby placing this protein within the context of a signaling pathway.

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Structural insights into the histidine-containing phosphotransfer protein and receiver domain of sensor histidine kinase suggest a complex model in the two-component regulatory system in Pseudomonas aeruginosa

IUCrJ ◽

10.1107/s2052252520009665 ◽

2020 ◽

Vol 7 (5) ◽

pp. 934-948

Author(s):

Shao-Kang Chen ◽

Hong-Hsiang Guan ◽

Pei-Hsun Wu ◽

Li-Ting Lin ◽

Meng-Chun Wu ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Active Site ◽

Histidine Kinase ◽

Convex Surface ◽

Complex Model ◽

Phosphoryl Group ◽

Chronic Infections ◽

Sensor Histidine Kinase ◽

Receiver Domain ◽

Two Component

In Pseudomonas aeruginosa, an important opportunistic pathogen that causes numerous acute and chronic infections, the hybrid two-component system (TCS) regulates the swarming ability and biofilm formation with a multistep phosphorelay, and consists of hybrid-sensor histidine kinase (HK), histidine-containing phosphotransfer protein (Hpt) and response regulator (RR). In this work, two crystal structures of HptB and the receiver domain of HK PA1611 (PA1611REC) of P. aeruginosa have been determined in order to elucidate their interactions for the transfer of the phosphoryl group. The structure of HptB folds into an elongated four-helix bundle – helices α2, α3, α4 and α5, covered by the short N-terminal helix α1. The imidazole side chain of the conserved active-site histidine residue His57, located near the middle of helix α3, protrudes from the bundle and is exposed to solvent. The structure of PA1611REC possesses a conventional (β/α)5 topology with five-stranded parallel β-sheets folded in the central region, surrounded by five α-helices. The divalent Mg2+ ion is located in the negatively charged active-site cleft and interacts with Asp522, Asp565 and Arg567. The HptB–PA1611REC complex is further modeled to analyze the binding surface and interactions between the two proteins. The model shows a shape complementarity between the convex surface of PA1611REC and the kidney-shaped HptB with fewer residues and a different network involved in interactions compared with other TCS complexes, such as SLN1-R1/YPD1 from Saccharomyces cerevisiae and AHK5RD/AHP1 from Arabidopsis thaliana. These structural results provide a better understanding of the TCS in P. aeruginosa and could potentially lead to the discovery of a new treatment for infection.

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Faculty Opinions recommendation of Catalytic scaffolds for phosphoryl group transfer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726652237.793524606 ◽

2016 ◽

Author(s):

Lynn Kamerlin ◽

Yashraj Kulkarni

Keyword(s):

Phosphoryl Group ◽

Group Transfer

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Interhelical H-Bonds Modulate the Activity of a Polytopic Transmembrane Kinase

Biomolecules ◽

10.3390/biom11070938 ◽

2021 ◽

Vol 11 (7) ◽

pp. 938

Author(s):

Juan Cruz Almada ◽

Ana Bortolotti ◽

Jean Marie Ruysschaert ◽

Diego de Mendoza ◽

María Eugenia Inda ◽

...

Keyword(s):

Histidine Kinase ◽

Adaptive Response ◽

Catalytic Domain ◽

Membrane Lipids ◽

Signal Transmission ◽

Expression System ◽

Lipid Homeostasis ◽

Transmembrane Helices ◽

Transmembrane Region

DesK is a Histidine Kinase that allows Bacillus subtilis to maintain lipid homeostasis in response to changes in the environment. It is located in the membrane, and has five transmembrane helices and a cytoplasmic catalytic domain. The transmembrane region triggers the phosphorylation of the catalytic domain as soon as the membrane lipids rigidify. In this research, we study how transmembrane inter-helical interactions contribute to signal transmission; we designed a co-expression system that allows studying in vivo interactions between transmembrane helices. By Alanine-replacements, we identified a group of polar uncharged residues, whose side chains contain hydrogen-bond donors or acceptors, which are required for the interaction with other DesK transmembrane helices; a particular array of H-bond- residues plays a key role in signaling, transmitting information detected at the membrane level into the cell to finally trigger an adaptive response.

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A Unique GTP-Dependent Sporulation Sensor Histidine Kinase in Bacillus anthracis

Journal of Bacteriology ◽

10.1128/jb.01184-08 ◽

2008 ◽

Vol 191 (3) ◽

pp. 687-692 ◽

Cited By ~ 11

Author(s):

Francesca Scaramozzino ◽

Andrea White ◽

Marta Perego ◽

James A. Hoch

Keyword(s):

Bacillus Anthracis ◽

Histidine Kinase ◽

Catalytic Domain ◽

Coiled Coil ◽

Reverse Reaction ◽

Forward Reaction ◽

Critical Signal ◽

Sensor Histidine Kinase ◽

Virulence Plasmids ◽

Kinase Catalytic Domain

ABSTRACT The Bacillus anthracis BA2291 gene codes for a sensor histidine kinase involved in the induction of sporulation. Genes for orthologs of the sensor domain of the BA2291 kinase exist in virulence plasmids in this organism, and these proteins, when expressed, inhibit sporulation by converting BA2291 to an apparent phosphatase of the sporulation phosphorelay. Evidence suggests that the sensor domains inhibit BA2291 by titrating its activating signal ligand. Studies with purified BA2291 revealed that this kinase is uniquely specific for GTP in the forward reaction and GDP in the reverse reaction. The G1 motif of BA2291 is highly modified from ATP-specific histidine kinases, and modeling this motif in the structure of the kinase catalytic domain suggested how guanine binds to the region. A mutation in the putative coiled-coil linker between the sensor domain and the catalytic domains was found to decrease the rate of the forward autophosphorylation reaction and not affect the reverse reaction from phosphorylated Spo0F. The results suggest that the activating ligand for BA2291 is a critical signal for sporulation and in a limited concentration in the cell. Decreasing the response to it either by slowing the forward reaction through mutation or by titration of the ligand by expressing the plasmid-encoded sensor domains switches BA2291 from an inducer to an inhibitor of the phosphorelay and sporulation.

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A High-Throughput Strategy for Recombinant Protein Expression and Solubility Screen in Escherichia coli : A Case of Sensor Histidine Kinase

Methods in Molecular Biology - Histidine Phosphorylation ◽

10.1007/978-1-4939-9884-5_2 ◽

2019 ◽

pp. 19-36 ◽

Cited By ~ 1

Author(s):

Agnieszka Szmitkowska ◽

Blanka Pekárová ◽

Jan Hejátko

Keyword(s):

Escherichia Coli ◽

Recombinant Protein ◽

Protein Expression ◽

High Throughput ◽

Histidine Kinase ◽

Recombinant Protein Expression ◽

Sensor Histidine Kinase

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Insights into histidine kinase activation mechanisms from the monomeric blue light sensor EL346

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1813586116 ◽

2019 ◽

Vol 116 (11) ◽

pp. 4963-4972 ◽

Cited By ~ 5

Author(s):

Igor Dikiy ◽

Uthama R. Edupuganti ◽

Rinat R. Abzalimov ◽

Peter P. Borbat ◽

Madhur Srivastava ◽

...

Keyword(s):

Blue Light ◽

Conformational Changes ◽

Histidine Kinase ◽

Structural Changes ◽

Molecular Mechanisms ◽

Catalytic Domain ◽

Response Regulator ◽

Phosphoryl Group ◽

Dark State ◽

Light Sensing

Translation of environmental cues into cellular behavior is a necessary process in all forms of life. In bacteria, this process frequently involves two-component systems in which a sensor histidine kinase (HK) autophosphorylates in response to a stimulus before subsequently transferring the phosphoryl group to a response regulator that controls downstream effectors. Many details of the molecular mechanisms of HK activation are still unclear due to complications associated with the multiple signaling states of these large, multidomain proteins. To address these challenges, we combined complementary solution biophysical approaches to examine the conformational changes upon activation of a minimal, blue-light–sensing histidine kinase from Erythrobacter litoralis HTCC2594, EL346. Our data show that multiple conformations coexist in the dark state of EL346 in solution, which may explain the enzyme’s residual dark-state activity. We also observe that activation involves destabilization of the helices in the dimerization and histidine phosphotransfer-like domain, where the phosphoacceptor histidine resides, and their interactions with the catalytic domain. Similar light-induced changes occur to some extent even in constitutively active or inactive mutants, showing that light sensing can be decoupled from activation of kinase activity. These structural changes mirror those inferred by comparing X-ray crystal structures of inactive and active HK fragments, suggesting that they are at the core of conformational changes leading to HK activation. More broadly, our findings uncover surprising complexity in this simple system and allow us to outline a mechanism of the multiple steps of HK activation.

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