Structural and biochemical characterization of ligand recognition by CysB, the master regulator of sulfate metabolism

Mittal, Monica; Singh, Appu Kumar; Kumaran, S.

doi:10.1016/j.biochi.2017.08.011

Cited by 14 publications

(11 citation statements)

References 44 publications

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“…B). Residues 86–324 within the CysB homologue of S. typhimurium forms a structure that binds NAS (Mittal et al ., ), which alters the activity of CysB as a transcription factor via allostery. In E. coli , certain amino acid substitutions within the inducer region impact the ability of CysB to regulate transcription of cys genes (Lochowska et al ., ).…”

Section: Resultsmentioning

confidence: 99%

Sulfur availability for Vibrio fischeri growth during symbiosis establishment depends on biogeography within the squid light organ

Wasilko

Larios-Valencia

Steingard

et al. 2019

Molecular Microbiology

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Summary The fitness of host‐associated microbes depends on their ability to access nutrients in vivo. Identifying these mechanisms is significant for understanding how microbes have evolved to fill specific ecological niches within a host. Vibrio fischeri is a bioluminescent bacterium that colonizes and proliferates within the light organ of the Hawaiian bobtail squid, which provides an opportunity to study how bacteria grow in vivo. Here, the transcription factor CysB is shown to be necessary for V. fischeri both to grow on several sulfur sources in vitro and to establish symbiosis with juvenile squid. CysB is also found to regulate several genes involved in sulfate assimilation and to contribute to the growth of V. fischeri on cystine, which is the oxidized form of cysteine. A mutant that grows on cystine but not sulfate could establish symbiosis, suggesting that V. fischeri acquires nutrients related to this compound within the host. Finally, CysB‐regulated genes are shown to be differentially expressed among the V. fischeri populations occupying the various colonization sites found within the light organ. Together, these results suggest the biogeography of V. fischeri populations within the squid light organ impacts the physiology of this symbiotic bacterium in vivo through CysB‐dependent gene regulation.

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Section: Resultsmentioning

confidence: 99%

Sulfur availability for Vibrio fischeri growth during symbiosis establishment depends on biogeography within the squid light organ

Wasilko

Larios-Valencia

Steingard

et al. 2019

Molecular Microbiology

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“…So far, the structures of only a few activator-type LTTRs have been reported, and a sliding dimer model was proposed to explain how effectors activate LTTRs (28)(29)(30)(31)(32)(33)(34)(35). The recent structures of the ligand-binding domain of CysB from Salmonella typhimurium reveal two distinct binding sites that are allosterically coupled by two inducers (42). The overall structures of the RDs of NdhR and CysB are similar, with an rmsd of 2.90 Å over 167 Cα atoms, although CysB has two additional C-terminal helices and an unstructured tail.…”

Section: Discussionmentioning

confidence: 99%

Coordinating carbon and nitrogen metabolic signaling through the cyanobacterial global repressor NdhR

Jiang

Wang

Sun

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The coordination of carbon and nitrogen metabolism is essential for bacteria to adapt to nutritional variations in the environment, but the underlying mechanism remains poorly understood. In autotrophic cyanobacteria, high CO levels favor the carboxylase activity of ribulose 1,5 bisphosphate carboxylase/oxygenase (RuBisCO) to produce 3-phosphoglycerate, whereas low CO levels promote the oxygenase activity of RuBisCO, leading to 2-phosphoglycolate (2-PG) production. Thus, the 2-PG level is reversely correlated with that of 2-oxoglutarate (2-OG), which accumulates under a high carbon/nitrogen ratio and acts as a nitrogen-starvation signal. The LysR-type transcriptional repressor NAD(P)H dehydrogenase regulator (NdhR) controls the expression of genes related to carbon metabolism. Based on genetic and biochemical studies, we report here that 2-PG is an inducer of NdhR, while 2-OG is a corepressor, as found previously. Furthermore, structural analyses indicate that binding of 2-OG at the interface between the two regulatory domains (RD) allows the NdhR tetramer to adopt a repressor conformation, whereas 2-PG binding to an intradomain cleft of each RD triggers drastic conformational changes leading to the dissociation of NdhR from its target DNA. We further confirmed the effect of 2-PG or 2-OG levels on the transcription of the NdhR regulon. Together with previous findings, we propose that NdhR can sense 2-OG from the Krebs cycle and 2-PG from photorespiration, two key metabolites that function together as indicators of intracellular carbon/nitrogen status, thus representing a fine sensor for the coordination of carbon and nitrogen metabolism in cyanobacteria.

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“…Although several results from previous studies have suggested that OAS is spontaneously converted to NAS in a pH-dependent manner (Flavin and Slaughter, 1967) and that NAS is the true signal for the Cys regulon (Ostrowski and Kredich, 1989;Hryniewicz and Kredich, 1994;Lynch et al, 1994), recent research of ligand recognition by CysB in Salmonella typhimurium has proposed that CysB has two distinct ligand-binding sites: site-1 for sulfate and NAS and site-2 for NAS and OAS. The OAS remodels site-1 by binding to site-2 to enhance the NAS-mediated activation through allosteric coupling between sites (Mittal et al, 2017). Furthermore, N,O-diacetylserine produced from OAS in Salmonella enterica may be the true signal for the Cys regulon (Vandrisse and Escalante-Semerena, 2018).…”

Section: Oas and N-acetylserine Regulate Transcription In Bacteria And Plantsmentioning

confidence: 99%

Metabolism and Regulatory Functions of O-Acetylserine, S-Adenosylmethionine, Homocysteine, and Serine in Plant Development and Environmental Responses

2021

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The metabolism of an organism is closely related to both its internal and external environments. Metabolites can act as signal molecules that regulate the functions of genes and proteins, reflecting the status of these environments. This review discusses the metabolism and regulatory functions of O-acetylserine (OAS), S-adenosylmethionine (AdoMet), homocysteine (Hcy), and serine (Ser), which are key metabolites related to sulfur (S)-containing amino acids in plant metabolic networks, in comparison to microbial and animal metabolism. Plants are photosynthetic auxotrophs that have evolved a specific metabolic network different from those in other living organisms. Although amino acids are the building blocks of proteins and common metabolites in all living organisms, their metabolism and regulation in plants have specific features that differ from those in animals and bacteria. In plants, cysteine (Cys), an S-containing amino acid, is synthesized from sulfide and OAS derived from Ser. Methionine (Met), another S-containing amino acid, is also closely related to Ser metabolism because of its thiomethyl moiety. Its S atom is derived from Cys and its methyl group from folates, which are involved in one-carbon metabolism with Ser. One-carbon metabolism is also involved in the biosynthesis of AdoMet, which serves as a methyl donor in the methylation reactions of various biomolecules. Ser is synthesized in three pathways: the phosphorylated pathway found in all organisms and the glycolate and the glycerate pathways, which are specific to plants. Ser metabolism is not only important in Ser supply but also involved in many other functions. Among the metabolites in this network, OAS is known to function as a signal molecule to regulate the expression of OAS gene clusters in response to environmental factors. AdoMet regulates amino acid metabolism at enzymatic and translational levels and regulates gene expression as methyl donor in the DNA and histone methylation or after conversion into bioactive molecules such as polyamine and ethylene. Hcy is involved in Met–AdoMet metabolism and can regulate Ser biosynthesis at an enzymatic level. Ser metabolism is involved in development and stress responses. This review aims to summarize the metabolism and regulatory functions of OAS, AdoMet, Hcy, and Ser and compare the available knowledge for plants with that for animals and bacteria and propose a future perspective on plant research.

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Structural and biochemical characterization of ligand recognition by CysB, the master regulator of sulfate metabolism

Cited by 14 publications

References 44 publications

Sulfur availability for Vibrio fischeri growth during symbiosis establishment depends on biogeography within the squid light organ

Sulfur availability for Vibrio fischeri growth during symbiosis establishment depends on biogeography within the squid light organ

Coordinating carbon and nitrogen metabolic signaling through the cyanobacterial global repressor NdhR

Metabolism and Regulatory Functions of O-Acetylserine, S-Adenosylmethionine, Homocysteine, and Serine in Plant Development and Environmental Responses

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