Snapshots of Conformational Changes Shed Light into the NtrX Receiver Domain Signal Transduction Mechanism

Fernández, Ignacio; Otero, Lisandro H.; Klinke, S.; Carrica, Mariela del Carmen; Goldbaum, Fernando A.

doi:10.1016/j.jmb.2015.06.010

Cited by 19 publications

(30 citation statements)

References 57 publications

(20 reference statements)

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“…This mechanism explains how Asp phosphorylation induces conformational changes at specific residues or structural elements that are propagated to the α4β5α5 surface, which is used by the OmpR/PhoB family to dimerize. However, this mechanism seems not be universal for RRs, since alternative mechanisms deferring for the Y-T coupling has been proposed ( 51 , 52 ). This would be in line with the observation of alternative dimerization surfaces in other RRs, suggesting that these RRs should not follow a canonical Y-T coupling mechanism, with final output effect involving modification of the α4β5α5 surface.…”

Section: Discussionmentioning

confidence: 99%

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator

Casino

Miguel-Romero

Huesa

et al. 2017

Nucleic Acids Research

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The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3−. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic.

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Section: Discussionmentioning

confidence: 99%

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator

Casino

Miguel-Romero

Huesa

et al. 2017

Nucleic Acids Research

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“…Such dimerization modes include the `5-5` dimer of HupR [135], the `4-5` dimer of FixJ and NtrX [136, 137] and the `4-5-5-6` dimer of spr1814 [138]. The latter might however be a crystallographic artifact as this author-identified dimer is inconsistent with computational predictions.…”

Section: Response Generationmentioning

confidence: 99%

“…Whether these regulatory mechanisms are representative for many RR remains to be seen. The above examples point to a continuous rather than a simple on/off mechanism for the transition from the inactive to the active conformation of the RR [137, 148]. …”

Section: Response Generationmentioning

confidence: 99%

Molecular Mechanisms of Two-Component Signal Transduction

Zschiedrich

Keidel

Szurmant

2016

Journal of Molecular Biology

438

364

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Two-component systems comprising sensor histidine kinases and response regulator proteins are among the most important players in bacterial and archaeal signal transduction and also occur in reduced numbers in some eukaryotic organisms. Given their importance to cellular survival, virulence and cellular development these systems are among the most scrutinized bacterial proteins. In recent years a flurry of bioinformatics, genetic, biochemical and structural studies have provided detailed insights into many of the molecular mechanisms that underlie the detection of signals and the generation of the appropriate response by two-component systems. Importantly, it has become clear that there is significant diversity in the mechanisms employed by individual systems. This review discusses the current knowledge on common themes and divergences from the paradigm of two-component system signaling. An emphasis is on the information gained by a flurry of recent structural and bioinformatics studies.

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“…The 3D structure of NtrX from B. abortus has been resolved by X-ray crystal diffraction (27,28). It was successfully used for reconstruction of 3D structures of NtrX from S. meliloti, Agrobacterium tumefacience and C. crescentus in Swiss-Model server.…”

Section: Phosphorylated Ntrx Regulates Cell Division Of Rhizobium Spementioning

confidence: 99%

Direct regulation of cell cycle regulatory gene expression by NtrX to promoteSinorhizobium meliloticell division

Xing

Huang

et al. 2020

Preprint

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In α-proteobacteria, the CtrA signaling pathway regulates cell cycle progression. A species whose cell duplication is associated with CtrA stability is affected by the response regulator NtrX. However, the function of NtrX acting on the cell cycle regulation in bacteria remains unclear. Here, we report that NtrX controls transcription of the CtrA system genes involved in cell cycle regulation in a legume symbiont, Sinorhizobium meliloti. Three groups of ntrX mutants showed the similar cell cycle defects, such as slow growth, abnormal shapes, and irregular genomic DNA accumulation. Expression of the CtrA signaling pathway genes including ctrA, gcrA, dnaA, divL and cpdR1, is differentially regulated by the phosphorylated NtrX protein. The regulation is achieved through direct protein-DNA interactions. The 53rd aspartate residue known as the conserved phosporylation site and located in the receiver domain of NtrX, is required for S. meliloti cell cycle regulation. Interestingly, expression of S. meliloti ntrX derivatives in Caulobacter and Agrobacterium strains showed distinct defects of cell duplication and growth, suggesting that NtrX plays different roles in cell cycle regulation in these bacteria. Our findings demonstrate that NtrX is an upstream transcriptional regulator of the CtrA signaling pathway in S. meliloti, which could be associated with nitrogen nutrient response.

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Snapshots of Conformational Changes Shed Light into the NtrX Receiver Domain Signal Transduction Mechanism

Cited by 19 publications

References 57 publications

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator

Molecular Mechanisms of Two-Component Signal Transduction

Direct regulation of cell cycle regulatory gene expression by NtrX to promoteSinorhizobium meliloticell division

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