4r24

Complete dissection of B. subtilis nitrogen homeostatic circuitry

spinqualitylabelsall models 4r24, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4r24 is a 2 chain structure with sequence from Priestia megaterium WSH-002 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TNRA_PRIMW Transcription regulator that actives the transcription of genes required for nitrogen assimilation during nitrogen limitation. On the contrary of the MerR members, which require longer DNA sites for high-affinity binding, TnrA requires a DNA sequence of 17 nucleotides as minimal binding site.[UniProtKB:Q45666] Publication Abstract from PubMed All cells must sense and adapt to changing nutrient availability. However, detailed molecular mechanisms coordinating such regulatory pathways remain poorly understood. In Bacillus subtilis, nitrogen homeostasis is controlled by a unique circuitry composed of the regulator TnrA, which is deactivated by feedback-inhibited glutamine synthetase (GS) during nitrogen excess and stabilized by GlnK upon nitrogen depletion, and the repressor GlnR. Here we describe a complete molecular dissection of this network. TnrA and GlnR, the global nitrogen homeostatic transcription regulators, are revealed as founders of a new structural family of dimeric DNA-binding proteins with C-terminal, flexible, effector-binding sensors that modulate their dimerization. Remarkably, the TnrA sensor domains insert into GS intersubunit catalytic pores, destabilizing the TnrA dimer and causing an unprecedented GS dodecamer-to-tetradecamer conversion, which concomitantly deactivates GS. In contrast, each subunit of the GlnK trimer "templates" active TnrA dimers. Unlike TnrA, GlnR sensors mediate an autoinhibitory dimer-destabilizing interaction alleviated by GS, which acts as a GlnR chaperone. Thus, these studies unveil heretofore unseen mechanisms by which inducible sensor domains drive metabolic reprograming in the model Gram-positive bacterium B. subtilis. Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis.,Schumacher MA, Chinnam NB, Cuthbert B, Tonthat NK, Whitfill T Genes Dev. 2015 Feb 15;29(4):451-64. doi: 10.1101/gad.254714.114. PMID:25691471 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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