Hexameric arginine repressor, ArgR, is the feedback regulator of bacterial L-arginine regulons, and sensor of L-arg that controls transcription of genes for its synthesis and catabolism. Although ArgR function, as well as its secondary, tertiary, and quaternary structures, is essentially the same in E. coli and B. subtilis, the two proteins differ significantly in sequence, including residues implicated in the response to L-arg. Molecular dynamics simulations are used here to evaluate the behavior of intact B. subtilis ArgR with and without L-arg, and are compared with prior MD results for a domain fragment of E. coli ArgR. Relative to its crystal structure, B. subtilis ArgR in absence of L-arg undergoes a large-scale rotational shift of its trimeric subassemblies that is very similar to that observed in the E. coli protein, but the residues driving rotation have distinct secondary and tertiary structural locations, and a key residue that drives rotation in E. coli is missing in B. subtilis. The similarity of trimer rotation despite different driving residues suggests that a rotational shift between trimers is integral to ArgR function. This conclusion is supported by phylogenetic analysis of distant ArgR homologs reported here that indicates at least three major groups characterized by distinct sequence motifs but predicted to undergo a common rotational transition. The dynamic consequences of L-arg binding for transcriptional activation of intact ArgR are evaluated here for the first time in two-microsecond simulations of B. subtilis ArgR. L-arg binding to intact B. subtilis ArgR causes a significant further shift in the angle of rotation between trimers that causes the N-terminal DNA-binding domains lose their interactions with the C-terminal domains, and is likely the first step toward adopting DNA-binding-competent conformations. The results aid interpretation of crystal structures of ArgR and ArgR-DNA complexes.

• MeSH
• alosterická regulace MeSH
• arginin chemie   metabolismus   MeSH
• Bacillus subtilis chemie   genetika   metabolismus   MeSH
• bakteriální proteiny chemie   genetika   metabolismus   MeSH
• entropie MeSH
• Escherichia coli chemie   genetika   metabolismus   MeSH
• fylogeneze MeSH
• konformace proteinů, alfa-helix MeSH
• konformace proteinů, beta-řetězec MeSH
• proteinové domény MeSH
• regulon genetika   MeSH
• represorové proteiny chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• simulace molekulární dynamiky MeSH
• vazba proteinů MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH

The membrane-embedded FtsH proteases found in bacteria, chloroplasts, and mitochondria are involved in diverse cellular processes including protein quality control and regulation. The genome of the model cyanobacterium Synechocystis sp PCC 6803 encodes four FtsH homologs designated FtsH1 to FtsH4. The FtsH3 homolog is present in two hetero-oligomeric complexes: FtsH2/3, which is responsible for photosystem II quality control, and the essential FtsH1/3 complex, which helps maintain Fe homeostasis by regulating the level of the transcription factor Fur. To gain a more comprehensive insight into the physiological roles of FtsH hetero-complexes, we performed genome-wide expression profiling and global proteomic analyses of Synechocystis mutants conditionally depleted of FtsH3 or FtsH1 grown under various nutrient conditions. We show that the lack of FtsH1/3 leads to a drastic reduction in the transcriptional response to nutrient stress of not only Fur but also the Pho, NdhR, and NtcA regulons. In addition, this effect is accompanied by the accumulation of the respective transcription factors. Thus, the FtsH1/3 complex is of critical importance for acclimation to iron, phosphate, carbon, and nitrogen starvation in Synechocystis.plantcell;31/12/2912/FX1F1fx1.

• MeSH
• aklimatizace genetika   MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• dusík nedostatek   metabolismus   MeSH
• exprese genu MeSH
• fosfáty nedostatek   metabolismus   MeSH
• fosforylace MeSH
• fotosystém II (proteinový komplex) chemie   genetika   metabolismus   MeSH
• metaloproteasy genetika   metabolismus   MeSH
• mutace MeSH
• proteiny vázající fosfáty genetika   metabolismus   MeSH
• proteolýza MeSH
• proteom genetika   metabolismus   MeSH
• proteomika MeSH
• regulace genové exprese u bakterií genetika   MeSH
• regulon genetika   MeSH
• represorové proteiny genetika   metabolismus   MeSH
• ribozomální proteiny genetika   metabolismus   MeSH
• Synechocystis enzymologie   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• uhlík nedostatek   metabolismus   MeSH
• živiny nedostatek   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Identifying regulons of sigma factors is a vital subtask of gene network inference. Integrating multiple sources of data is essential for correct identification of regulons and complete gene regulatory networks. Time series of expression data measured with microarrays or RNA-seq combined with static binding experiments (e.g., ChIP-seq) or literature mining may be used for inference of sigma factor regulatory networks. RESULTS: We introduce Genexpi: a tool to identify sigma factors by combining candidates obtained from ChIP experiments or literature mining with time-course gene expression data. While Genexpi can be used to infer other types of regulatory interactions, it was designed and validated on real biological data from bacterial regulons. In this paper, we put primary focus on CyGenexpi: a plugin integrating Genexpi with the Cytoscape software for ease of use. As a part of this effort, a plugin for handling time series data in Cytoscape called CyDataseries has been developed and made available. Genexpi is also available as a standalone command line tool and an R package. CONCLUSIONS: Genexpi is a useful part of gene network inference toolbox. It provides meaningful information about the composition of regulons and delivers biologically interpretable results.

• MeSH
• Bacteria genetika   MeSH
• časové faktory MeSH
• databáze genetické * MeSH
• Eukaryota genetika   MeSH
• genové regulační sítě * MeSH
• lidé MeSH
• regulace genové exprese * MeSH
• regulon genetika   MeSH
• reprodukovatelnost výsledků MeSH
• Saccharomyces cerevisiae genetika   MeSH
• software * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH