Evidence map›Paper›PMID 24733389›Full record

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.

Wei Lin, Ying Wang, Xiaobiao Han, Zilong Zhang, Chengyuan Wang, Jin Wang, Huaiyu Yang, Yinhua Lu, Weihong Jiang, Guo-Ping Zhao and 1 more

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.7field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Orphan response regulator NnaR is critical for nitrate and nitrite assimilation inFrontiers in cellular and infection microbiology · 2024
    Article
  5. 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 · 2023
    Article
  6. Article
  7. Review
  8. Two-Component Systems ofInternational journal of molecular sciences · 2022
    Review
  9. Article
  10. Journal of natural products · 2022
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. TheMicrobiology (Reading, England) · 2017
    Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 1 country.

Wei LinFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology.
Ying WangFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology, the State Key Laboratory of Genetic Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Xiaobiao HanFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology.
Zilong ZhangFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology.
Chengyuan WangState Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
Jin WangFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology.
Huaiyu Yangthe Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yinhua LuFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology.
Weihong JiangFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology.
Guo-Ping ZhaoFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology, the State Key Laboratory of Genetic Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China, the Shanghai-MOST Key Laboratory of Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China, the Department of Microbiology and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China, and gpzhao@sibs.ac.cn.
Peng ZhangFrom the Chinese Academy of Sciences Key Laboratory of Synthetic Biology, State Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China, pengzhang01@sibs.ac.cn.
Chinese Academy of Sciences · CNCenter for Excellence in Molecular Plant Sciences · CNState Key Laboratory of Synthetic Chemistry · CNFudan University · CNShanghai Institute of Materia Medica · CNState Key Laboratory of Genetic Engineering

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

ActinomycetalesAmino Acid SequenceAspartic AcidBacterial ProteinsCrystallography, X-RayDimerizationGene Expression Regulation, BacterialMolecular Sequence DataMycobacterium tuberculosisPhosphorylationStreptomyces coelicolorStructure-Activity RelationshipTrans-ActivatorsAspartic AcidBacterial ProteinsGlnR protein, Streptomyces coelicolorosmolarity response regulator proteinsPhoB protein, BacteriaTrans-ActivatorsActinobacteriaCrystal StructureGene RegulationHomodimerOmpR/PhoB SubfamilyPhosphorylationProtein ConformationReceiver DomainUnphosphorylated Aspartate

Identifiers

PMID24733389
PMCPMC4140898
OpenAlexW2050995302

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.