4S0R

Structure of GS-TnrA complex

Summary for 4S0R

• Entry DOI: 10.2210/pdb4s0r/pdb
• Descriptor: Glutamine synthetase, TnrA peptide, GLUTAMINE, ... (4 entities in total)
• Functional Keywords: glutamine synthesis, transcription regulation, chaperone, ligase
• Biological source: Bacillus subtilis
• Cellular location: Cytoplasm : P12425
• Total number of polymer chains: 28
• Total formula weight: 738434.29

Authors

Schumacher, M.A.,Chinnam, N.G.,Cuthbert, B.,Tonthat, N.K. (deposition date: 2015-01-04, release date: 2015-03-04, Last modification date: 2024-02-28)

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 (3.5 Å)