Cooperation of Secondary Transporters and Sensor Kinases in Transmembrane Signalling

Unden, Gottfried; Wörner, Sebastian; Monzel, Christian

doi:10.1016/bs.ampbs.2016.02.003

Cited by 21 publications

(17 citation statements)

References 96 publications

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“…Notwithstanding, there are remarkable differences between the Mae1 group and other previously characterized TCS, most notably, the presence of a degenerated CA domain in the MaeK-like sensor proteins, which precludes MaeK ATP-dependent autophosphorylation. Furthermore, in characterized sensor kinases of this family, a cognate transporter usually functions as a co-sensor 23 , but apparently this is not the case for MaeK since the absence of L-malate transporters did not affect the induction of mae genes 19 .…”

Section: Discussionmentioning

confidence: 99%

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The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates

Miguel-Romero

Casino

Landete

et al. 2017

Sci Rep

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Microbial colonization of different environments is enabled to a great extent by the plasticity of their sensory mechanisms, among them, the two-component signal transduction systems (TCS). Here, an example of TCS plasticity is presented: the regulation of L-malate catabolism via malic enzyme by MaeRK in Lactobacillales. MaeKR belongs to the citrate family of TCS as the Escherichia coli DcuSR system. We show that the Lactobacillus casei histidine-kinase MaeK is defective in autophosphorylation activity as it lacks a functional catalytic and ATP binding domain. The cognate response regulator MaeR was poorly phosphorylated at its phosphoacceptor Asp in vitro. This phosphorylation, however, enhanced MaeR binding in vitro to its target sites and it was required for induction of regulated genes in vivo. Elucidation of the MaeR structure revealed that response regulator dimerization is accomplished by the swapping of α4-β5-α5 elements between two monomers, generating a phosphoacceptor competent conformation. Sequence and phylogenetic analyses showed that the MaeKR peculiarities are not exclusive to L. casei as they are shared by the rest of orthologous systems of Lactobacillales. Our results reveal MaeKR as a non-canonical TCS displaying distinctive features: a swapped response regulator and a sensor histidine kinase lacking ATP-dependent kinase activity.

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Section: Discussionmentioning

confidence: 99%

“…This result, together with the absence of genes encoding putative solute binding proteins, suggests that no co-sensor proteins are participating in the regulation of MaeK activity, in contrast to other TCS of the citrate family (e.g. DcuS) 23 .…”

Section: Introductionmentioning

confidence: 94%

The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates

Miguel-Romero

Casino

Landete

et al. 2017

Sci Rep

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“…Among those, E. coli and B. subtilis C4 transporters are some of the best-characterized for auxiliary functions in signal transduction. In particular, the C4-dicarboxylate/orotate symporter DctA, which is a polarly localized non-ABC C4-carbohydrate transporter in E. coli (Scheu et al, 2014;Unden et al, 2016) and similarly in B. subtilis (Groeneveld et al, 2010;Graf et al, 2014), can form a sensory unit with a transmembrane sensor kinase. In E. coli this is the protein DcuS of the DcuS/DcuR TCS (Monzel et al, 2013).…”

Section: Regulatory Influence Of Membrane Transport Proteins and Intrmentioning

confidence: 99%

Protein Activity Sensing in Bacteria in Regulating Metabolism and Motility

2020

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Bacteria have evolved complex sensing and signaling systems to react to their changing environments, most of which are present in all domains of life. Canonical bacterial sensing and signaling modules, such as membrane-bound ligand-binding receptors and kinases, are very well described. However, there are distinct sensing mechanisms in bacteria that are less studied. For instance, the sensing of internal or external cues can also be mediated by changes in protein conformation, which can either be implicated in enzymatic reactions, transport channel formation or other important cellular functions. These activities can then feed into pathways of characterized kinases, which translocate the information to the DNA or other response units. This type of bacterial sensory activity has previously been termed protein activity sensing. In this review, we highlight the recent findings about this non-canonical sensory mechanism, as well as its involvement in metabolic functions and bacterial motility. Additionally, we explore some of the specific proteins and protein-protein interactions that mediate protein activity sensing and their downstream effects. The complex sensory activities covered in this review are important for bacterial navigation and gene regulation in their dynamic environment, be it host-associated, in microbial communities or free-living.

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“…nutrients, toxins) across the membrane (Tetsch and Jung, ; Piepenbreier et al ., ). As such, transporters can affect HK activity indirectly by altering the concentration of the signaling substrate and/or directly through a protein‐protein interaction with the HK that affects the phosphotransfer process (Witan et al ., ; Dintner et al ., ; Unden et al ., ). Proteins lacking enzymatic activity can also affect the phosphotransfer process through interactions with either the HK or RR (Mitrophanov and Groisman, ; Buelow and Raivio, ).…”

Section: Introductionmentioning

confidence: 99%

“…While there is much to learn regarding the physiological function and regulatory mechanisms of accessory regulators, well‐characterized examples point to regulatory complexity not easily attainable with a HK alone. This includes mechanisms for (i) the combinatorial integration of distinct signaling inputs (Cangelosi et al ., ; Unden et al ., ), (ii) establishing regulatory connections between seemingly independent regulatory pathways (Kato and Groisman, ; Eguchi et al ., ; Gerken et al ., ), (iii) altering the sensitivity of the HK for its cognate inducers (Cangelosi et al ., ), (iv) directly sensing nutrient scavenging or detoxification functions (e.g. flux sensing (Fritz et al ., ; Piepenbreier et al ., )) and (v) fine‐tuning response dynamics of the TCS (e.g.…”

Section: Introductionmentioning

confidence: 99%

The UzcRS two‐component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators

Park

Overton

Jiao

2019

Molecular Microbiology

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Summary The UzcRS two‐component system in Caulobacter crescentus mediates widespread transcriptional activation in response to the metals U, Zn and Cu. Unexpectedly, a screen for mutations that affected the activity of the UzcR‐regulated urcA promoter (PurcA) revealed four previously uncharacterized proteins whose inactivation led to metal‐independent induction of PurcA. Using molecular genetics and functional genomics, we find that these auxiliary regulators control PurcA expression by modulating the activity of UzcRS through distinct mechanisms. An ABC transporter with a periplasmic metallo‐aminopeptidase domain forms a sensory complex with UzcRS, antagonizing metal dependent stimulation by virtue of its ATPase and peptidase domains. Two MarR‐like transcription factors synergistically regulate UzcRS activity by repressing the expression of the membrane proteins UzcY and UzcZ, which stimulate UzcRS activity and enhance its sensitivity to a more environmentally relevant U/Zn/Cu concentration range. Additionally, the membrane protein UzcX, whose expression is positively regulated by UzcR, provides a mechanism of feedback inhibition within the UzcRS circuit. Collectively, these data suggest that UzcRS functions as the core‐signaling unit within a multicomponent signal transduction pathway that includes a diverse set of auxiliary regulators, providing further insight into the complexity of signaling networks.

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Cooperation of Secondary Transporters and Sensor Kinases in Transmembrane Signalling

Cited by 21 publications

References 96 publications

The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates

The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates

Protein Activity Sensing in Bacteria in Regulating Metabolism and Motility

The UzcRS two‐component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators

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