Structural highlights
Function
[GLNR_BACSU] Represses many genes including the glnRA operon and tnrA during growth with nitrogen excess.[1] [2] [3]
Publication Abstract from PubMed
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.
Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria.,Travis BA, Peck JV, Salinas R, Dopkins B, Lent N, Nguyen VD, Borgnia MJ, Brennan RG, Schumacher MA Nat Commun. 2022 Jul 1;13(1):3793. doi: 10.1038/s41467-022-31573-0. PMID:35778410[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fisher SH. Regulation of nitrogen metabolism in Bacillus subtilis: vive la difference! Mol Microbiol. 1999 Apr;32(2):223-32. PMID:10231480
- ↑ Nakano Y, Kimura K. Purification and characterization of a repressor for the Bacillus cereus glnRA operon. J Biochem. 1991 Feb;109(2):223-8. PMID:1677938
- ↑ Schreier HJ, Brown SW, Hirschi KD, Nomellini JF, Sonenshein AL. Regulation of Bacillus subtilis glutamine synthetase gene expression by the product of the glnR gene. J Mol Biol. 1989 Nov 5;210(1):51-63. PMID:2573733
- ↑ Travis BA, Peck JV, Salinas R, Dopkins B, Lent N, Nguyen VD, Borgnia MJ, Brennan RG, Schumacher MA. Molecular dissection of the glutamine synthetase-GlnR nitrogen regulatory circuitry in Gram-positive bacteria. Nat Commun. 2022 Jul 1;13(1):3793. doi: 10.1038/s41467-022-31573-0. PMID:35778410 doi:http://dx.doi.org/10.1038/s41467-022-31573-0
