7tdv
Crystal structure of S. aureus glutamine synthetase in Met-Sox-P/ADP transition state complex
Structural highlights
FunctionE3VXC2_STAAU Glutamine synthetase (GS) is an unusual multitasking protein that functions as an enzyme, a transcription coregulator, and a chaperone in ammonium assimilation and in the regulation of genes involved in nitrogen metabolism. It catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia. Feedback-inhibited GlnA also interacts with and regulates the activity of the transcriptional regulator TnrA. During nitrogen limitation, TnrA is in its DNA-binding active state and turns on the transcription of genes required for nitrogen assimilation. Under conditions of nitrogen excess, feedback-inhibited GlnA forms a stable complex with TnrA, which inhibits its DNA-binding activity. In contrast, feedback-inhibited GlnA acts as a chaperone to stabilize the DNA-binding activity of GlnR, which represses the transcription of nitrogen assimilation genes.[ARBA:ARBA00002161] Publication Abstract from PubMedHow 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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