ArticleThe Journal of biological chemistry2014
Atypical OmpR/PhoB subfamily response regulator GlnR of actinomycetes functions as a homodimer, stabilized by the unphosphorylated conserved Asp-focused charge interactions.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- A clarifying perspective on bacterial pseudo-receiver domains.Journal of bacteriology · 2025Review
- The global nitrogen regulator GlnR is a direct transcriptional repressor of the key gluconeogenic geneJournal of bacteriology · 2024Article
- Multifaceted regulation of siderophore synthesis by multiple regulatory systems in Shewanella oneidensis.Communications biology · 2024Article
- Orphan response regulator NnaR is critical for nitrate and nitrite assimilation inFrontiers in cellular and infection microbiology · 2024Article
- Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural basis of phosphorylation-induced activation of the response regulator VbrR.Acta biochimica et biophysica Sinica · 2023Article
- Research progress on GlnR-mediated regulation in Actinomycetes.Frontiers in microbiology · 2023Review
- Two-Component Systems ofInternational journal of molecular sciences · 2022Review
- Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria.Nature communications · 2022Article
- Review
- Modulation of Gene Expression in Actinobacteria by Translational Modification of Transcriptional Factors and Secondary Metabolite Biosynthetic Enzymes.Frontiers in microbiology · 2021Review
- A recently evolved diflavin-containing monomeric nitrate reductase is responsible for highly efficient bacterial nitrate assimilation.The Journal of biological chemistry · 2020Article
- GlnR Dominates Rifamycin Biosynthesis by Activating theFrontiers in microbiology · 2020Article
- The Balance Metabolism Safety Net: Integration of Stress Signals by Interacting Transcriptional Factors inFrontiers in microbiology · 2019Review
- Insight into the Molecular Mechanism of the Transcriptional Regulation ofFrontiers in microbiology · 2018Article
- TheMicrobiology (Reading, England) · 2017Article
- To ∼P or Not to ∼P? Non-canonical activation by two-component response regulators.Molecular microbiology · 2017Review
- Post-translational Serine/Threonine Phosphorylation and Lysine Acetylation: A Novel Regulatory Aspect of the Global Nitrogen Response Regulator GlnR in S. coelicolor M145.Frontiers in molecular biosciences · 2016Article
- GlnR-Mediated Regulation of ectABCD Transcription Expands the Role of the GlnR Regulon to Osmotic Stress Management.Journal of bacteriology · 2015Article
- Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress.Molecular microbiology · 2015Article
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The OmpR/PhoB subfamily protein GlnR of actinomycetes is an orphan response regulator that globally coordinates the expression of genes related to nitrogen metabolism. Biochemical and genetic analyses reveal that the functional GlnR from Amycolatopsis mediterranei is unphosphorylated at the potential phosphorylation Asp(50) residue in the N-terminal receiver domain. The crystal structure of this receiver domain demonstrates that it forms a homodimer through the α4-β5-α5 dimer interface highly similar to the phosphorylated typical response regulator, whereas the so-called "phosphorylation pocket" is not conserved, with its space being occupied by an Arg(52) from the β3-α3 loop. Both in vitro and in vivo experiments confirm that GlnR forms a functional homodimer via its receiver domain and suggest that the charge interactions of Asp(50) with the highly conserved Arg(52) and Thr(9) in the receiver domain may be crucial in maintaining the proper conformation for homodimerization, as also supported by molecular dynamics simulations of the wild type GlnR versus the deficient mutant GlnR(D50A). This model is backed by the distinct phenotypes of the total deficient GlnR(R52A/T9A) double mutant versus the single mutants of GlnR (i.e. D50N, D50E, R52A and T9A), which have only minor effects upon both dimerization and physiological function of GlnR in vivo, albeit their DNA binding ability is weakened compared with that of the wild type. By integrating the supportive data of GlnRs from the model Streptomyces coelicolor and the pathogenic Mycobacterium tuberculosis, we conclude that the actinomycete GlnR is atypical with respect to its unphosphorylated conserved Asp residue being involved in the critical Arg/Asp/Thr charge interactions, which is essential for maintaining the biologically active homodimer conformation.
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