One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas
| Autor: | Simona Pepe, Eleftheria Trampari, Rowena K. Y. Fung, Davide Roncarati, Govind Chandra, Lucia Grenga, Richard Little, Rosaria Campilongo, Jacob G. Malone, Clare E. M. Stevenson |
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| Přispěvatelé: | Campilongo, Rosaria, Fung, Rowena K. Y., Little, Richard H., Grenga, Lucia, Trampari, Eleftheria, Pepe, Simona, Chandra, Govind, Stevenson, Clare E. M., Roncarati, Davide, Malone, Jacob G. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Glycerol
0301 basic medicine Cancer Research Transcription Factor Regulator Gene Expression Ligands Biochemistry Database and Informatics Methods Glucose Metabolism Pyruvic Acid Transcriptional regulation Genetics (clinical) Protein Metabolism Regulation of gene expression biology Glyoxylates Ketones Chemistry Physical Sciences Carbohydrate Metabolism Sequence Analysis Gluconeogenesi Metabolic Networks and Pathways Research Article Pyruvate Pseudomonas Fluorescens lcsh:QH426-470 Bioinformatics 030106 microbiology Glyoxylate cycle Bacterial Protein Pseudomonas fluorescens Ligand Monomers (Chemistry) Research and Analysis Methods Gluconates Glyoxylate 03 medical and health sciences Gluconate Bacterial Proteins Genetic Gene Types Sequence Motif Analysis Pseudomonas Genetics Polymer chemistry Binding site Transcription factor Molecular Biology Ecology Evolution Behavior and Systematics Binding Sites Bacteria Pseudomonas fluorescen Gluconeogenesis Chemical Compounds Organisms Binding Site Biology and Life Sciences Metabolic Networks and Pathway Gene Expression Regulation Bacterial biology.organism_classification Ecology Evolution Behavior and Systematic Carbon lcsh:Genetics Metabolism 030104 developmental biology Glucose Regulator Genes Acids Transcription Factors |
| Zdroj: | PLoS Genetics, Vol 13, Iss 6, p e1006839 (2017) PLoS Genetics |
| Popis: | Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate. Author summary Here we show how Pseudomonas controls multiple different primary carbon metabolism pathways by sensing levels of KDPG, an Entner Doudoroff (ED) pathway intermediate. KDPG binds to two highly similar transcription factors; the ED regulator HexR and the previously uncharacterised protein RccR. RccR inversely controls the glyoxylate shunt, gluconeogenesis and pyruvate metabolism, suppressing the first two pathways as pyruvate metabolism genes are expressed, and vice versa. This complex regulation is enabled by two distinct RccR-binding consensus sequences in the RccR regulon promoters. KDPG binding simultaneously increases RccR affinity for the glyoxylate shunt and gluconeogenesis promoters, and releases repression of pyruvate metabolism. This elegant two-regulator circuit allows Pseudomonas to rapidly respond to carbon source availability by sensing a single key intermediate, KDPG. |
| Databáze: | OpenAIRE |
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