Ligand-Induced Folding of a Two-Component Signaling Receiver Domain

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.

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

Molecular Biology of the Cell ◽

10.1091/mbc.01-09-0434 ◽

2002 ◽

Vol 13 (2) ◽

pp. 412-424 ◽

Cited By ~ 69

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.

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Clock-associated genes in Arabidopsis : a family affair

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2001.0965 ◽

2001 ◽

Vol 356 (1415) ◽

pp. 1745-1753 ◽

Cited By ~ 35

Author(s):

David E. Somers

Keyword(s):

Transcription Factor ◽

Circadian Clock ◽

Gene Families ◽

Forward Genetics ◽

Pas Domain ◽

Receiver Domain ◽

Domain Structures ◽

Two Component ◽

Similarities And Differences ◽

Signalling Systems

The identification of components of the plant circadian clock has been advanced recently with the success of two forward genetics approaches. The ZEITLUPE and TOC1 loci were cloned and each was found to be part of two separate, larger gene families with intriguing domain structures. The ZTL family of proteins contains a subclass of the PAS domain coupled to an F box and kelch motifs, suggesting that they play a role in a novel light–regulated ubiquitination mechanism. TOC1 shares similarity to the receiver domain of the well–known two–component phosphorelay signalling systems, combined with a strong similarity to a region of the CONSTANS transcription factor, which is involved in controlling flowering time. When added to the repertoire of previously identified clock–associated genes, it is clear that both similarities and differences with other circadian systems will emerge in the coming years.

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Crystal Structure of the Response Regulator 02 Receiver Domain, the Essential YycF Two-Component System of Streptococcus pneumoniae in both Complexed and Native States

Journal of Bacteriology ◽

10.1128/jb.186.9.2872-2879.2004 ◽

2004 ◽

Vol 186 (9) ◽

pp. 2872-2879 ◽

Cited By ~ 33

Author(s):

Colin J. Bent ◽

Neil W. Isaacs ◽

Timothy J. Mitchell ◽

Alan Riboldi-Tunnicliffe

Keyword(s):

Streptococcus Pneumoniae ◽

Active Site ◽

Response Regulator ◽

Thermotoga Maritima ◽

Two Component System ◽

Environmental Signals ◽

Receiver Domain ◽

Two Component ◽

Protein Sequence Homology ◽

Two Component Signal Transduction

ABSTRACT A variety of bacterial cellular responses to environmental signals are mediated by two-component signal transduction systems comprising a membrane-associated histidine protein kinase and a cytoplasmic response regulator (RR), which interpret specific stimuli and produce a measured physiological response. In RR activation, transient phosphorylation of a highly conserved aspartic acid residue drives the conformation changes needed for full activation of the protein. Sequence homology reveals that RR02 from Streptococcus pneumoniae belongs to the OmpR subfamily of RRs. The structures of the receiver domains from four members of this family, DrrB and DrrD from Thermotoga maritima, PhoB from Escherichia coli, and PhoP from Bacillus subtilis, have been elucidated. These domains are globally very similar in that they are composed of a doubly wound α5β5; however, they differ remarkably in the fine detail of the β4-α4 and α4 regions. The structures presented here reveal a further difference of the geometry in this region. RR02 is has been shown to be the essential RR in the gram-positive bacterium S. pneumoniae R. Lange, C. Wagner, A. de Saizieu, N. Flint, J. Molnos, M. Stieger, P. Caspers, M. Kamber, W. Keck, and K. E. Amrein, Gene 237:223-234, 1999; J. P. Throup, K. K. Koretke, A. P. Bryant, K. A. Ingraham, A. F. Chalker, Y. Ge, A. Marra, N. G. Wallis, J. R. Brown, D. J. Holmes, M. Rosenberg, and M. K. Burnham, Mol. Microbiol. 35:566-576, 2000). RR02 functions as part of a phosphotransfer system that ultimately controls the levels of competence within the bacteria. Here we report the native structure of the receiver domain of RR02 from serotype 4 S. pneumoniae (as well as acetate- and phosphate-bound forms) at different pH levels. Two native structures at 2.3 Å, phased by single-wavelength anomalous diffraction (xenon SAD), and 1.85 Å and a third structure at pH 5.9 revealed the presence of a phosphate ion outside the active site. The fourth structure revealed the presence of an acetate molecule in the active site.

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Two‐component signaling in the AAA+ ATPase DctD: binding Mg 2+ and BeF 3 selects between alternative dimeric states of the receiver domain

The FASEB Journal ◽

10.1096/fj.02-0395fje ◽

2002 ◽

Vol 16 (14) ◽

pp. 1964-1966 ◽

Cited By ~ 43

Author(s):

Sungdae Park ◽

Matthew Meyer ◽

A. Daniel Jones ◽

Hemant P. Yennawar ◽

Neela H. Yennawar ◽

...

Keyword(s):

Aaa Atpase ◽

Receiver Domain ◽

Two Component

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Cross Talk Inhibition Nullified by a Receiver Domain Missense Substitution

Journal of Bacteriology ◽

10.1128/jb.00436-15 ◽

2015 ◽

Vol 197 (20) ◽

pp. 3294-3306 ◽

Cited By ~ 3

Author(s):

TuAnh Ngoc Huynh ◽

Hsia-Yin Lin ◽

Chris E. Noriega ◽

Alice V. Lin ◽

Valley Stewart

Keyword(s):

Cross Talk ◽

Response Regulator ◽

Bacterial Species ◽

Sensor Response ◽

Acetate Metabolism ◽

Receiver Domain ◽

Two Component ◽

High Interaction ◽

High Level

ABSTRACTIn two-component signal transduction, a sensor protein transmitter module controls cognate receiver domain phosphorylation. Most receiver domain sequences contain a small residue (Gly or Ala) at position T + 1 just distal to the essential Thr or Ser residue that forms part of the active site. However, some members of the NarL receiver subfamily have a large hydrophobic residue at position T + 1. Our laboratory previously isolated a NarL mutant in which the T + 1 residue Val-88 was replaced with an orthodox small Ala. This NarL V88A mutant confers a striking phenotype in which high-level target operon expression is both signal (nitrate) and sensor (NarX and NarQ) independent. This suggests that the NarL V88A protein is phosphorylated by cross talk from noncognate sources. Although cross talk was enhanced inackAnull strains that accumulate acetyl phosphate, it persisted inpta ackAdouble null strains that cannot synthesize this compound and was observed also innarL+strains. This indicates that acetate metabolism has complex roles in mediating NarL cross talk. Contrariwise, cross talk was sharply diminished in anarcB barAdouble null strain, suggesting that the encoded sensors contribute substantially to NarL V88A cross talk. Separately, the V88A substitution altered thein vitrorates of NarL autodephosphorylation and transmitter-stimulated dephosphorylation and decreased affinity for the cognate sensor, NarX. Together, these experiments show that the residue at position T + 1 can strongly influence two distinct aspects of receiver domain function, the autodephosphorylation rate and cross talk inhibition.IMPORTANCEMany bacterial species contain a dozen or more discrete sensor-response regulator two-component systems that convert a specific input into a distinct output pattern. Cross talk, the unwanted transfer of signals between circuits, occurs when a response regulator is phosphorylated inappropriately from a noncognate source. Cross talk is inhibited in part by the high interaction specificity between cognate sensor-response regulator pairs. This study shows that a relatively subtle missense change from Val to Ala nullifies cross talk inhibition, enabling at least two noncognate sensors to enforce an inappropriate output independently of the relevant input.

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Feedback control of a two-component signaling system by an Fe-S-binding receiver domain

10.1101/729053 ◽

2019 ◽

Author(s):

Benjamin J. Stein ◽

Aretha Fiebig ◽

Sean Crosson

Keyword(s):

Feedback Control ◽

Histidine Kinase ◽

Oxygen Sensor ◽

Cell Physiology ◽

Environmental Cues ◽

Sensor Kinase ◽

Signaling System ◽

Receiver Domain ◽

Two Component ◽

Feedback Inhibitor

AbstractTwo-component signaling systems (TCSs) function to detect environmental cues and transduce this information into a change in transcription. In its simplest form, TCS-dependent regulation of transcription entails phosphoryl-transfer from a sensory histidine kinase to its cognate DNA-binding receiver protein. However, in certain cases, auxiliary proteins may modulate TCSs in response to secondary environmental cues. Caulobacter crescentus FixT is one such auxiliary regulator. FixT is composed of a single receiver domain and functions as a feedback inhibitor of the FixL-FixJ (FixLJ) TCS, which regulates the transcription of genes involved in adaptation to microaerobiosis. We sought to define the impact of fixT on Caulobacter cell physiology and to understand the molecular mechanism by which FixT represses FixLJ signaling. fixT deletion results in excess production of porphyrins and premature entry into stationary phase, demonstrating the importance of feedback inhibition of the FixLJ signaling system. Although FixT is a receiver domain, it does not affect dephosphorylation of the oxygen-sensor kinase FixL or phosphoryltransfer from FixL to its cognate receiver FixJ. Rather, FixT represses FixLJ signaling by inhibiting the FixL autophosphorylation reaction. We have further identified a 4-cysteine motif in Caulobacter FixT that binds an Fe-S cluster and protects the protein from degradation by the Lon protease. Our data support a model in which oxidation of this Fe-S cluster promotes degradation of FixT in vivo. This proteolytic mechanism facilitates clearance the of the FixT feedback inhibitor from the cell under normoxia and resets the FixLJ system for a future microaerobic signaling event.ImportanceTwo-component signal transduction systems (TCSs) are broadly conserved in the bacterial kingdom and generally contain two molecular components: a sensor histidine kinase and a receiver protein. Sensor histidine kinases alter their phosphorylation state in direct response to a physical or chemical cue, whereas receiver proteins “receive” the phosphoryl group from the kinase to regulate a change in cell physiology. We have discovered that a single-domain receiver protein, FixT, binds an Fe-S cluster and controls Caulobacter heme homeostasis though its function as a negative feedback regulator of the oxygen-sensor kinase, FixL. We provide evidence that the Fe-S cluster protects FixT from Lon-dependent proteolysis in the cell and endows FixT with the ability to function as a second, autonomous oxygen/redox sensor in the FixL-FixJ signaling pathway. This study introduces a novel mechanism of regulated TCS feedback control by an Fe-S-binding receiver domain.

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