4R4E

Structure of GlnR-DNA complex

Summary for 4R4E

• Entry DOI: 10.2210/pdb4r4e/pdb
• Descriptor: HTH-type transcriptional regulator GlnR, DNA (5'-D(*AP*TP*TP*CP*TP*GP*AP*CP*A)-3'), DNA (5'-D(*TP*GP*TP*CP*AP*GP*TP*A)-3'), ... (5 entities in total)
• Functional Keywords: tnra/glnr family, b. subtilis, nitrogen homeostasis, new member, tnra/glnr dna-binding family of winged-hth with c-terminal inducer/sensor domain, transcription, dna, gs-q, nucleoid, transcription regulator-dna complex, transcription regulator/dna
• Biological source: Bacillus subtilis subsp. subtilis; More
• Total number of polymer chains: 4
• Total formula weight: 24744.25

Authors

Schumacher, M.A. (deposition date: 2014-08-19, release date: 2015-03-04, Last modification date: 2024-04-03)

Primary citation

Schumacher, M.A.,Chinnam, N.B.,Cuthbert, B.,Tonthat, N.K.,Whitfill, T.
Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis.
Genes Dev., 29:451-464, 2015

PubMed Abstract: 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.

PubMed: 25691471
DOI: 10.1101/gad.254714.114

Experimental method

X-RAY DIFFRACTION (2.57 Å)