Structure and function of HWE/HisKA2-family sensor histidine kinases

Herrou, Julien; Crosson, Sean; Fiebig, Aretha

doi:10.1016/j.mib.2017.01.008

Cited by 30 publications

(43 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At the center of this pathway is the PhyR protein, comprising a C‐terminal receiver (REC) domain and an N‐terminal σ‐like (SL) domain (Francez‐Charlot et al ., ; Herrou et al ., ). In the current structural model, aspartyl phosphorylation in the PhyR REC domain by a sensor kinase (Lourenco et al ., ; Kim et al ., ; Kaczmarczyk et al ., ; Herrou et al ., ), induces a conformational change that enables binding of the anti‐σ EcfG factor NepR to the PhyR SL domain. This process releases the extracytoplasmic function (ECF) σ‐factor, σ EcfG , to bind RNA polymerase and control gene expression (Fig.…”

Section: Introductionmentioning

confidence: 99%

Allosteric control of a bacterial stress response system by an anti‐σ factor

Luebke

Eaton

Sachleben

et al. 2017

Molecular Microbiology

Self Cite

View full text Add to dashboard Cite

Bacterial signal transduction systems commonly use receiver (REC) domains, which regulate adaptive responses to the environment as a function of their phosphorylation state. REC domains control cell physiology through diverse mechanisms, many of which remain understudied. We have defined structural features that underlie activation of the multi-domain REC protein, PhyR, which functions as an anti-anti-σ factor and regulates transcription of genes required for stress adaptation and host-microbe interactions in Alphaproteobacteria. Though REC phosphorylation is necessary for PhyR function in vivo, we did not detect expected changes in inter-domain interactions upon phosphorylation by solution X-ray scattering. We sought to understand this result by defining additional molecular requirements for PhyR activation. We uncovered specific interactions between unphosphorylated PhyR and an intrinsically disordered region (IDR) of the anti-σ factor, NepR, by solution NMR spectroscopy. Our data support a model whereby nascent NepR(IDR)-PhyR interactions and REC phosphorylation coordinately impart the free energy to shift PhyR to an open, active conformation that binds and inhibits NepR. This mechanism ensures PhyR is activated only when NepR and an activating phosphoryl signal are present. Our study provides new structural understanding of the molecular regulatory logic underlying a conserved environmental response system.

show abstract

Section: Introductionmentioning

confidence: 99%

Allosteric control of a bacterial stress response system by an anti‐σ factor

Luebke

Eaton

Sachleben

et al. 2017

Molecular Microbiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The class Alphaproteobacteria contains species that inhabit diverse ecological niches, and that have a significant impact on nutrient cycling, agricultural production and human health (Batut et al, 2004). Alphaproteobacteria commonly encode proteins that contain a LOV domain coupled to an HWE/HisKA2-type (Herrou et al, 2017) histidine kinase. Surprisingly, these "LOV-HWE kinases" are often present in heterotrophic species with no evident photobiology (Herrou & Crosson, 2011).…”

Section: Lov-hwe Kinases: An Overviewmentioning

confidence: 99%

“…Surprisingly, these "LOV-HWE kinases" are often present in heterotrophic species with no evident photobiology (Herrou & Crosson, 2011). Histidine kinases are typically co-expressed with and phosphorylate their cognate response regulators to directly control gene expression (Hoch & Silhavy, 1995), but HWE/HisKA2 kinases are unusual in that they are often orphaned on the bacterial chromosome, or are adjacent to single domain response regulators (SDRR) that lack a regulatory output domain to control gene expression (Herrou et al, 2017).…”

Section: Lov-hwe Kinases: An Overviewmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of theErythrobacter litoralisDSM 8509 general stress response by visible light

Fiebig

Varesio

Navarreto³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Extracytoplasmic function (ECF) sigma factors are a major class of environmentallyresponsive transcriptional regulators. In Alphaproteobacteria the ECF sigma factor, σ EcfG , activates general stress response (GSR) transcription and protects cells from multiple stressors. A phosphorylation-dependent protein partner switching mechanism, involving HWE/HisKA_2-family histidine kinases, underlies σ EcfG activation. The identity of these sensor kinases and the signals that regulate them remain largely uncharacterized. We have developed the aerobic anoxygenic photoheterotrophic (AAP) bacterium, Erythrobacter litoralis DSM 8509, as a comparative genetic model to investigate GSR regulation. Using this system, we sought to define the contribution of visible light and a photosensory HWE kinase, LovK, to GSR transcription. We identified three HWE kinases that collectively regulate GSR: gsrK and lovK are activators, while gsrP is a repressor. GSR transcription is higher in the dark than light, and the opposing activities of gsrK and gsrP are sufficient to achieve light-dependent differential transcription. In the absence of gsrK and gsrP, lovK alone is sufficient to regulate GSR transcription in response to light. This regulation requires a photochemically active LOV domain in LovK. Our studies establish a role for visible light and HWE kinases in lightdependent regulation of GSR transcription in E. litoralis, an AAP species. GRAPHICAL ABSTRACT ABBREVIATED SUMMARYGeneral stress response (GSR) systems protect bacteria from a diverse range of physical and chemical stressors. We have developed Erythrobacter litoralis as a new genetic model to study GSR in Alphaproteobacteria and show that three HWE-family histidine kinases collectively regulate GSR transcription via σ EcfG . Visible light is a GSR regulatory signal in E. litoralis, and LovK is a blue-light photosensor kinase that functions as a dark activated GSR regulator.

show abstract

“…Another potential site for HKIII dimerization is the periplasmic four-helix bundle domain, which is also known to dimerize in conventional MCPs (16). Finally, some cytoplasmic histidine kinases are known to be able to function as monomers (37)(38)(39), and this might be the case for HKIIIs.…”

Section: Class III Histidine Kinasesmentioning

confidence: 99%

Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility

et al. 2017

View full text Add to dashboard Cite

Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIIIcontaining genomes also contain pilT, a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design.IMPORTANCE Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.KEYWORDS chemotaxis, evolution, genomics, histidine kinase, motility, pathogens, signal transduction, type IV pili T he transmission of molecular signals in prokaryotes is carried out by the specialized cellular machinery. The simplest signal transduction systems consist of a single protein that is capable of both sensing a signal and directly affecting a cellular

show abstract

Structure and function of HWE/HisKA2-family sensor histidine kinases

Cited by 30 publications

References 56 publications

Allosteric control of a bacterial stress response system by an anti‐σ factor

Allosteric control of a bacterial stress response system by an anti‐σ factor

Regulation of theErythrobacter litoralisDSM 8509 general stress response by visible light

Class III Histidine Kinases: a Recently Accessorized Kinase Domain in Putative Modulators of Type IV Pilus-Based Motility

Contact Info

Product

Resources

About