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Title | Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 3793, Year 2022 |
Publish date | Jul 1, 2022 |
![]() | Brady A Travis / Jared V Peck / Raul Salinas / Brandon Dopkins / Nicholas Lent / Viet D Nguyen / Mario J Borgnia / Richard G Brennan / Maria A Schumacher / ![]() |
PubMed Abstract | How bacteria sense and respond to nitrogen levels are central questions in microbial physiology. In Gram-positive bacteria, nitrogen homeostasis is controlled by an operon encoding glutamine ...How bacteria sense and respond to nitrogen levels are central questions in microbial physiology. In Gram-positive bacteria, nitrogen homeostasis is controlled by an operon encoding glutamine synthetase (GS), a dodecameric machine that assimilates ammonium into glutamine, and the GlnR repressor. GlnR detects nitrogen excess indirectly by binding glutamine-feedback-inhibited-GS (FBI-GS), which activates its transcription-repression function. The molecular mechanisms behind this regulatory circuitry, however, are unknown. Here we describe biochemical and structural analyses of GS and FBI-GS-GlnR complexes from pathogenic and non-pathogenic Gram-positive bacteria. The structures show FBI-GS binds the GlnR C-terminal domain within its active-site cavity, juxtaposing two GlnR monomers to form a DNA-binding-competent GlnR dimer. The FBI-GS-GlnR interaction stabilizes the inactive GS conformation. Strikingly, this interaction also favors a remarkable dodecamer to tetradecamer transition in some GS, breaking the paradigm that all bacterial GS are dodecamers. These data thus unveil unique structural mechanisms of transcription and enzymatic regulation. |
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Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.96 - 3.5 Å |
Structure data | EMDB-25863, PDB-7tf6: EMDB-25864, PDB-7tf7: EMDB-25866, PDB-7tf9: EMDB-25867, PDB-7tfa: EMDB-25868, PDB-7tfb: EMDB-25869, PDB-7tfc: EMDB-25870, PDB-7tfd: EMDB-25871, PDB-7tfe: ![]() PDB-7tdp: ![]() PDB-7tdv: ![]() PDB-7tea: ![]() PDB-7tec: ![]() PDB-7ten: |
Chemicals | ![]() ChemComp-ADP: ![]() ChemComp-P3S: ![]() ChemComp-MG: ![]() ChemComp-HOH: ![]() ChemComp-SO4: ![]() ChemComp-CA: ![]() ChemComp-GLN: |
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