Diversity of two-component systems: insights into the signal transduction mechanism by the Staphylococcus aureus two-component system GraSR

Muzamal, Uzma; Gómez, Daniel E.; Kapadia, Fenika; Golemi-Kotra, Dasantila

doi:10.12688/f1000research.5512.2

Cited by 17 publications

(9 citation statements)

References 25 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accessory proteins that stimulate histidine kinase autophosphorylation are often transmembrane proteins, which interact with kinase domains facing the membrane or the periplasm (Gerken & Misra, ; Eguchi et al ., ). A few cytoplasmic proteins that activate TCSs are known, including GraX in S. aureus and UspC in E. coli , which act through scaffolding of cognate kinase‐response regulator complexes (Heermann et al ., ; Falord et al ., ; Muzamal et al ., ). It remains to be investigated, whether PtsN is just the tip on an iceberg of similarly acting accessory proteins that interact directly with the kinase DHp domain and can be easily recruited to regulate additional kinases either positively or negatively.…”

Section: Discussionmentioning

confidence: 97%

Non‐canonical activation of histidine kinase KdpD by phosphotransferase protein PtsN through interaction with the transmitter domain

Mörk-Mörkenstein

Heermann

Göpel

et al. 2017

Molecular Microbiology

View full text Add to dashboard Cite

The two-component system KdpD/KdpE governs K homeostasis by controlling synthesis of the high affinity K transporter KdpFABC. When sensing low environmental K concentrations, the dimeric kinase KdpD autophosphorylates in trans and transfers the phosphoryl-group to the response regulator KdpE, which subsequently activates kdpFABC transcription. In Escherichia coli, KdpD can also be activated by interaction with the non-phosphorylated form of the accessory protein PtsN. PtsN stimulates KdpD kinase activity thereby increasing phospho-KdpE levels. Here, we analyzed the interplay between KdpD/KdpE and PtsN. PtsN binds specifically to the catalytic DHp domain of KdpD, which is also contacted by KdpE. Accordingly, PtsN and KdpE compete for binding, providing a paradox. Low levels of non-phosphorylated PtsN stimulate, whereas high amounts reduce kdpFABC expression by blocking access of KdpE to KdpD. Ligand fishing experiments provided insight as they revealed ternary complex formation of PtsN/KdpD /KdpE in vivo demonstrating that PtsN and KdpE bind different protomers in the KdpD dimer. PtsN may bind one protomer to stimulate phosphorylation of the second KdpD protomer, which then phosphorylates bound KdpE. Phosphorylation of PtsN prevents its incorporation in ternary complexes. Interaction with the conserved DHp domain enables PtsN to regulate additional kinases such as PhoR.

show abstract

Section: Discussionmentioning

confidence: 97%

Non‐canonical activation of histidine kinase KdpD by phosphotransferase protein PtsN through interaction with the transmitter domain

Mörk-Mörkenstein

Heermann

Göpel

et al. 2017

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…Interestingly, evidence has emerged recently suggesting that TCS–TCS direct interactions may sometimes be independent of the phosphorelay and at other times act as signal transducers for interacting proteins. ,,− Hybrid HisKs are able to function alone or in conjunction with diverse cognate and noncognate partners to form signaling complexes. − The involvement of multiple hybrid HisKs such as RetS, LadS, and PA1611 in the GacA/S-Rsm regulatory pathway in P. aeruginosa is unique.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Direct Interaction between Hybrid Sensor Kinases PA1611 and RetS That Controls Biofilm Formation and the Type III Secretion System in Pseudomonas aeruginosa

Bhagirath

Pydi

et al. 2016

ACS Infect. Dis.

View full text Add to dashboard Cite

One of the leading causes of morbidity and mortality in cystic fibrosis (CF) patients is pulmonary infection with Pseudomonas aeruginosa, and the pathophysiology of pulmonary infection in CF is affected by the lifestyle of this micro-organism. RetS-GacS/A-RsmA is a key regulatory pathway in P. aeruginosa that determines the bacterium’s lifestyle choice. Previously, we identified PA1611, a hybrid sensor kinase, as a new player in this pathway that interacts with RetS and influences biofilm formation and type III secretion system. In this study, we explored the structural and mechanistic basis of the interaction between PA1611 and RetS. We identified the amino acid residues critical for PA1611–RetS interactions by molecular modeling. These residues were then targeted for site-directed mutagenesis. Amino acid substitutions were carried out at seven key positions in PA1611 and at six corresponding key positions in RetS. The influence of such substitutions in PA1611 on the interaction was analyzed by bacterial two-hybrid assays. We carried out functional analysis of these mutants in P. aeruginosa for their effect on specific phenotypes. Two residues, F269 and E276, located within the histidine kinase A and histidine kinase-like ATPase domains of PA1611 were found to play crucial roles in the PA1611–RetS interaction and had profound effects on phenotypes. Corresponding mutations in RetS demonstrated similar results. We further confirmed that these mutations in PA1611 function through the GacS/GacA-RsmY/Z signaling pathway. Collectively, our findings provide a noncognate sensor kinase direct interaction model for a signaling pathway, key for lifestyle selection in P. aeruginosa, and targeting such interaction may serve as a novel way of controlling infections with P. aeruginosa.

show abstract

“…Besides B. subtilis, similar complex activity sensing systems to detect the presence of antibiotics or antimicrobial peptides, exist in other Gram-positive Firmicutes (Ouyang et al, 2010;Coumes-Florens et al, 2011;Dintner et al, 2011;Muzamal et al, 2014). In fact, the impact of ABC transporters on TCS sensing may be FIGURE 1 | General scheme of the canonical chemotactic sensing and signaling pathway in the bacterial membrane for governing motility functions, which are also accessible for protein activity sensing.…”

Section: Regulatory Influence Of Membrane Transport Proteins and Intrmentioning

confidence: 99%

Protein Activity Sensing in Bacteria in Regulating Metabolism and Motility

2020

View full text Add to dashboard Cite

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.

show abstract

Diversity of two-component systems: insights into the signal transduction mechanism by the Staphylococcus aureus two-component system GraSR

Abstract: The response to cationic antimicrobial peptides

Cited by 17 publications

References 25 publications

Non‐canonical activation of histidine kinase KdpD by phosphotransferase protein PtsN through interaction with the transmitter domain

Non‐canonical activation of histidine kinase KdpD by phosphotransferase protein PtsN through interaction with the transmitter domain

Characterization of the Direct Interaction between Hybrid Sensor Kinases PA1611 and RetS That Controls Biofilm Formation and the Type III Secretion System in Pseudomonas aeruginosa

Protein Activity Sensing in Bacteria in Regulating Metabolism and Motility

Contact Info

Product

Resources

About