Histidine kinases from bacteria to humans

2013 ◽  
Vol 41 (4) ◽  
pp. 1023-1028 ◽  
Author(s):  
Paul V. Attwood
Keyword(s):  
Histidine Kinase ◽  
Tyrosine Kinases ◽  
Mitochondrial Enzymes ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Two Component ◽  
Higher Eukaryotes ◽  
Histidine Phosphorylation ◽  
Eukaryotic Organisms ◽  
Nucleoside Diphosphate Kinases

It is more than 50 years since protein histidine phosphorylation was first discovered in 1962 by Boyer and co-workers; however, histidine kinases are still much less well recognized than the serine/threonine and tyrosine kinases. The best-known histidine kinases are the two-component signalling kinases that occur in bacteria, fungi and plants. The mechanisms and functions of these kinases, their cognate response regulators and associated phosphorelay proteins are becoming increasingly well understood. When genomes of higher eukaryotes began to be sequenced, it did not appear that they contained two-component histidine kinase system homologues, apart from a couple of related mitochondrial enzymes that were later shown not to function as histidine kinases. However, as a result of the burgeoning sequencing of genomes from a wide variety of eukaryotic organisms, it is clear that there are proteins that correspond to components of the two-component histidine kinase systems in higher eukaryotes and that operational two-component kinase systems are likely to occur in these organisms. There is unequivocal direct evidence that protein histidine phosphorylation does occur in mammals. So far, only nucleoside diphosphate kinases have been shown to be involved in protein histidine phosphorylation, but their mechanisms of action are not well understood. It is clear that other, yet to be identified, histidine kinases also exist in mammals and that protein histidine phosphorylation may play important roles in higher eukaryotes.

scholarly journals Predicted Functional and Structural Diversity of Receiver Domains in Fungal Two-Component Regulatory Systems

mSphere ◽  
2021 ◽  
Author(s):  
Robert B. Bourret ◽  
Clay A. Foster ◽  
William E. Goldman
Keyword(s):  
Structural Diversity ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Receiver Domain ◽  
Regulatory Systems ◽  
Two Component

Fungal two-component regulatory systems incorporate receiver domains into hybrid histidine kinases (HHKs) and response regulators. We constructed a nonredundant database of 670 fungal receiver domain sequences from 51 species sampled from nine fungal phyla.

Histidine kinases in signal transduction pathways of eukaryotes

1997 ◽  
Vol 110 (10) ◽  
pp. 1141-1145 ◽  
Author(s):  
W.F. Loomis ◽  
G. Shaulsky ◽  
N. Wang
Keyword(s):  
Signal Transduction ◽  
Response Regulator ◽  
Signal Transduction Pathways ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Camp Phosphodiesterase ◽  
Wide Range ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Dependent Protein

Autophosphorylating histidine kinases are an ancient conserved family of enzymes that are found in eubacteria, archaebacteria and eukaryotes. They are activated by a wide range of extracellular signals and transfer phosphate moieties to aspartates found in response regulators. Recent studies have shown that such two-component signal transduction pathways mediate osmoregulation in Saccharomyces cerevisiae, Dictyostelium discoideum and Neurospora crassa. Moreover, they play pivotal roles in responses of Arabidopsis thaliana to ethylene and cytokinin. A transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium cells aggregate during development. Activation of DhkA results in the inhibition of its response regulator, RegA, which is a cAMP phosphodiesterase that regulates the cAMP dependent protein kinase PKA. When PKA is activated late in the differentiation of prespore cells, they encapsulate into spores. There is evidence that this two-component system participates in a feedback loop linked to PKA in prestalk cells such that the signal to initiate encapsulation is rapidly amplified. Such signal transduction pathways can be expected to be found in a variety of eukaryotic differentiations since they are rapidly reversible and can integrate disparate signals.

scholarly journals Cyanobacterial Two-Component Proteins: Structure,Diversity, Distribution, andEvolution

2006 ◽  
Vol 70 (2) ◽  
pp. 472-509 ◽  
Author(s):  
Mark K. Ashby ◽  
Jean Houmard
Keyword(s):  
Regulatory Mechanisms ◽  
Genome Plasticity ◽  
Cyanobacterial Genome ◽  
Response Regulators ◽  
Genome Sequences ◽  
Histidine Kinases ◽  
Physiological Properties ◽  
Two Component ◽  
Different Strains ◽  
Structure Diversity

SUMMARY A survey of the already characterized and potential two-component protein sequences that exist in the nine complete and seven partially annotated cyanobacterial genome sequences available (as of May 2005) showed that the cyanobacteria possess a much larger repertoire of such proteins than most other bacteria. By analysis of the domain structure of the 1,171 potential histidine kinases, response regulators, and hybrid kinases, many various arrangements of about thirty different modules could be distinguished. The number of two-component proteins is related in part to genome size but also to the variety of physiological properties and ecophysiologies of the different strains. Groups of orthologues were defined, only a few of which have representatives with known physiological functions. Based on comparisons with the proposed phylogenetic relationships between the strains, the orthology groups show that (i) a few genes, some of them clustered on the genome, have been conserved by all species, suggesting their very ancient origin and an essential role for the corresponding proteins, and (ii) duplications, fusions, gene losses, insertions, and deletions, as well as domain shuffling, occurred during evolution, leading to the extant repertoire. These mechanisms are put in perspective with the different genetic properties that cyanobacteria have to achieve genome plasticity. This review is designed to serve as a basis for orienting further research aimed at defining the most ancient regulatory mechanisms and understanding how evolution worked to select and keep the most appropriate systems for cyanobacteria to develop in the quite different environments that they have successfully colonized.

scholarly journals Antifungal Properties and Target Evaluation of Three Putative Bacterial Histidine Kinase Inhibitors

1999 ◽  
Vol 43 (7) ◽  
pp. 1700-1703 ◽  
Author(s):  
Robert J. Deschenes ◽  
Hong Lin ◽  
Addison D. Ault ◽  
Jan S. Fassler
Keyword(s):  
Histidine Kinase ◽  
Drug Targets ◽  
Kinase Inhibitors ◽  
Inhibitory Concentration ◽  
Drug Efficacy ◽  
Antibacterial Drug ◽  
Histidine Kinases ◽  
Antifungal Properties ◽  
Two Component

ABSTRACT Histidine protein kinases have been explored as potential antibacterial drug targets. The recent identification of two-component histidine kinases in fungi has led us to investigate the antifungal properties of three bacterial histidine kinase inhibitors (RWJ-49815, RWJ-49968, and RWJ-61907). All three compounds were found to inhibit growth of the Saccharomyces cerevisiae and Candida albicans strains, with MICs ranging from 1 to 20 μg/ml. However, deletion of SLN1, the only histidine kinase inS. cerevisiae, did not alter drug efficacy. In vitro kinase assays were performed by using the Sln1 histidine kinase purified from bacteria as a fusion protein to glutathione S-transferase. RWJ-49815 and RWJ-49968 inhibited kinase a 50% inhibitory concentration of 10 μM, whereas RWJ-61907 failed to inhibit at concentrations up to 100 μM. Based on these results, we conclude that these compounds have antifungal properties; however, their mode of action appears to be independent of histidine kinase inhibition.

scholarly journals The Eukaryotic Two-Component Histidine Kinase Sln1p RegulatesOCH1via the Transcription Factor, Skn7p

2002 ◽  
Vol 13 (2) ◽  
pp. 412-424 ◽  
Author(s):  
Sheng Li ◽  
Susan Dean ◽  
Zhijian Li ◽  
Joe Horecka ◽  
Robert J. Deschenes ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Osmotic Stress ◽  
Binding Site ◽  
Histidine Kinase ◽  
Response Regulators ◽  
Hog Pathway ◽  
Receiver Domain ◽  
Osmotic Response ◽  
Two Component

The yeast “two-component” osmotic stress phosphorelay consists of the histidine kinase, Sln1p, the phosphorelay intermediate, Ypd1p and two response regulators, Ssk1p and Skn7p, whose activities are regulated by phosphorylation of a conserved aspartyl residue in the receiver domain. Dephospho-Ssk1p leads to activation of the hyper-osmotic response (HOG) pathway, whereas phospho-Skn7p presumably leads to activation of hypo-osmotic response genes. The multifunctional Skn7 protein is important in oxidative as well as osmotic stress; however, the Skn7p receiver domain aspartate that is the phosphoacceptor in the SLN1 pathway is dispensable for oxidative stress. Like many well-characterized bacterial response regulators, Skn7p is a transcription factor. In this report we investigate the role of Skn7p in osmotic response gene activation. Our studies reveal that the Skn7p HSF-like DNA binding domain interacts with acis-acting element identified upstream ofOCH1 that is distinct from the previously defined HSE-like Skn7p binding site. Our data support a model in which Skn7p receiver domain phosphorylation affects transcriptional activation rather than DNA binding to this class of DNA binding site.

scholarly journals Molecular Characterization of Two-Component Systems of Helicobacter pylori

2000 ◽  
Vol 182 (8) ◽  
pp. 2068-2076 ◽  
Author(s):  
Dagmar Beier ◽  
Rainer Frank
Keyword(s):  
Helicobacter Pylori ◽  
Histidine Kinase ◽  
Response Regulator ◽  
Response Regulators ◽  
Reading Frame ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

ABSTRACT Two-component systems are frequently involved in the adaptation of bacteria to changing environmental conditions at the level of transcriptional regulation. Here we report the characterization of members of the two-component systems of the gastric pathogenHelicobacter pylori deduced from the genome sequence of strain 26695. We demonstrate that the response regulators HP166, HP1043, and HP1021 have essential functions, as disruption of the corresponding genes is lethal for the bacteria, irrespective of the fact that HP1043 and HP1021 have nonconserved substitutions in crucial amino acids of their receiver domains. An analysis of the in vitro phosphorylation properties of the two-component proteins demonstrates that HP244-HP703 and HP165-HP166 are cognate histidine kinase-response regulator pairs. Furthermore, we provide evidence that the variability of the histidine kinase HP165 caused by a poly(C) tract of variable length close to the 3′ end of open reading frame 165/164 does not interfere with the kinase activity of the transmitter domain of HP165.

scholarly journals Blue Light Regulated Two-Component Systems: Enzymatic and Functional Analyses of Light-Oxygen-Voltage (LOV)-Histidine Kinases and Downstream Response Regulators

Biochemistry ◽  
2013 ◽  
Vol 52 (27) ◽  
pp. 4656-4666 ◽  
Author(s):  
Fernando Correa ◽  
Wen-Huang Ko ◽  
Victor Ocasio ◽  
Roberto A. Bogomolni ◽  
Kevin H. Gardner
Keyword(s):  
Blue Light ◽  
Response Regulators ◽  
Histidine Kinases ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Functional Analyses

scholarly journals The Anaplasma phagocytophilum PleC Histidine Kinase and PleD Diguanylate Cyclase Two-Component System and Role of Cyclic Di-GMP in Host Cell Infection

2008 ◽  
Vol 191 (3) ◽  
pp. 693-700 ◽  
Author(s):  
Tzung-Huei Lai ◽  
Yumi Kumagai ◽  
Mamoru Hyodo ◽  
Yoshihiro Hayakawa ◽  
Yasuko Rikihisa
Keyword(s):  
Histidine Kinase ◽  
Anaplasma Phagocytophilum ◽  
Kinase Domain ◽  
Etiologic Agent ◽  
Diguanylate Cyclase ◽  
Response Regulators ◽  
Cell Infection ◽  
Granulocytic Anaplasmosis ◽  
Two Component

ABSTRACT Anaplasma phagocytophilum, the etiologic agent of human granulocytic anaplasmosis (HGA), has genes predicted to encode three sensor kinases, one of which is annotated PleC, and three response regulators, one of which is PleD. Prior to this study, the roles of PleC and PleD in the obligatory intracellular parasitism of A. phagocytophilum and their biochemical activities were unknown. The present study illustrates the relevance of these factors by demonstrating that both pleC and pleD were expressed in an HGA patient. During A. phagocytophilum development in human promyelocytic HL-60 cells, PleC and PleD were synchronously upregulated at the exponential growth stage and downregulated prior to extracellular release. A recombinant PleC kinase domain (rPleCHKD) has histidine kinase activity; no activity was observed when the conserved site of phosphorylation was replaced with alanine. A recombinant PleD (rPleD) has autokinase activity using phosphorylated rPleCHKD as the phosphoryl donor but not with two other recombinant histidine kinases. rPleCHKD could not serve as the phosphoryl donor for a mutant rPleD (with a conserved aspartic acid, the site of phosphorylation, replaced by alanine) or two other A. phagocytophilum recombinant response regulators. rPleD had diguanylate cyclase activity to generate cyclic (c) di-GMP from GTP in vitro. UV cross-linking of A. phagocytophilum lysate with c-di-[32P]GMP detected an ∼47-kDa endogenous protein, presumably c-di-GMP downstream receptor. A new hydrophobic c-di-GMP derivative, 2′-O-di(tert-butyldimethylsilyl)-c-di-GMP, inhibited A. phagocytophilum infection in HL-60 cells. Our results suggest that the two-component PleC-PleD system is a diguanylate cyclase and that a c-di-GMP-receptor complex regulates A. phagocytophilum intracellular infection.

scholarly journals Two-Component Response Regulators Ssk1p and Skn7p Additively Regulate High-Osmolarity Adaptation and Fungicide Sensitivity in Cochliobolus heterostrophus

2006 ◽  
Vol 6 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Kosuke Izumitsu ◽  
Akira Yoshimi ◽  
Chihiro Tanaka
Keyword(s):  
Histidine Kinase ◽  
Response Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Cochliobolus Heterostrophus ◽  
Response Regulators ◽  
Fungicide Sensitivity ◽  
High Osmolarity ◽  
Group Iii ◽  
Two Component ◽  
Moderate Resistance

ABSTRACT Filamentous ascomycetous fungi possess many histidine kinases and two conserved response regulators, Ssk1p and Skn7p, in their two-component signaling systems. We previously reported that the fungus unique group III histidine kinase regulates high-osmolarity adaptation and iprodione/fludioxonil fungicide sensitivity by controlling the phosphorylation of Hog1-type mitogen-activated protein kinase (MAPK) in filamentous ascomycetes. Here, we have characterized the response regulator genes ChSsk1 and ChSkn7 in the southern corn leaf blight fungus Cochliobolus heterostrophus. Both ChSsk1- and ChSkn7-disrupted mutants showed little sensitivity to high-osmolarity stress and moderate resistance to the iprodione/fludioxonil fungicides. The phosphorylation of Hog1-type MAPK BmHog1p induced by high-osmolarity stress and fungicide treatments was only regulated by ChSsk1p, indicating that ChSkn7p has roles in high-osmolarity adaptation and fungicide sensitivity that are independent from the activation of BmHog1p. The Chssk1 Chskn7 double mutants clearly showed higher sensitivity to osmolar stress and higher resistance to fungicides than the single mutants. The dose responses of the double mutants fit well with those of the group III histidine kinase-deficient strain. These results suggest that in filamentous ascomycetes, the Ssk1- and Skn7-type response regulators control high-osmolarity adaptation and fungicide sensitivity additively with differential mechanisms under the regulation of the group III histidine kinase. This study provides evidence that filamentous fungi have a unique two-component signaling system that is different from that of yeast and is responsible for high-osmolarity adaptation and fungicide sensitivity.

scholarly journals Oligomeric states in sodium ion–dependent regulation of cyanobacterial histidine kinase-2

2017 ◽  
Author(s):  
Iskander M. Ibrahim ◽  
Liang Wang ◽  
Sujith Puthiyaveetil ◽  
Norbert Krauß ◽  
Jon Nield ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Histidine Kinase ◽  
Phosphate Group ◽  
Sodium Ion ◽  
Ion Concentration ◽  
Phosphoryl Transfer ◽  
Chemical Crosslinking ◽  
Response Regulators ◽  
Oligomeric State ◽  
Two Component

ABSTRACTTwo-component signal transduction systems (TCSs) consist of sensor histidine kinases and response regulators. TCSs mediate adaptation to environmental changes in bacteria, plants, fungi, and protists. Histidine kinase 2 (Hik2) is a sensor histidine kinase found in all known cyanobacteria and as chloroplast sensor kinase in eukaryotic algae and plants. Sodium ions have been shown to inhibit the autophosphorylation activity of Hik2 that precedes phosphoryl transfer to response regulators, but the mechanism of inhibition has not been determined. We report on the mechanism of Hik2 activation and inactivation probed by chemical crosslinking and size exclusion chromatography together with direct visualisation of the kinase using negative-stain transmission electron microscopy of single particles. We show that the functional form of Hik2 is a higher order oligomer such as a hexamer or octamer. Increased NaCl concentration converts the active hexamer into an inactive tetramer. Furthermore, the action of NaCl appears to be confined to the Hik2 kinase domain.IMPORTANCEBacteria sense change and respond to it by means of two-component regulatory systems. The sensor component is a protein that becomes covalently modified by a phosphate group on a histidine side chain. The response regulator accepts the phosphate group onto an aspartate, with structural and functional consequences, often for gene transcription. Histidine kinase 2 is a sensor of sodium ion concentration and redox potential, regulating transcription of genes for light-harvesting and reaction center proteins of photosynthesis in cyanobacteria and chloroplasts of algae and plants. Using radiolabeling, chemical crosslinking, chromatography and electron microscopy, we find that sodium ion concentration governs the oligomeric state of Histidine Kinase 2 and its phosphorylation by ATP.

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