4R24

Complete dissection of B. subtilis nitrogen homeostatic circuitry

4R24 の概要

• エントリーDOI: 10.2210/pdb4r24/pdb
• 関連するPDBエントリー: 4R22 4R25
• 分子名称: HTH-type transcriptional regulator TnrA, DNA (5'-D(*CP*GP*TP*GP*TP*AP*AP*GP*GP*AP*AP*TP*TP*CP*TP*GP*AP*CP*AP*CP*G)-3') (3 entities in total)
• 機能のキーワード: tnra, gs, b. subtilis, glnk, new dna-binding family, with winged hth, transcription, nucleoid, transcrption-dna complex, transcrption/dna
• 由来する生物種: Bacillus megaterium; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16524.71

構造登録者

Schumacher, M.A. (登録日: 2014-08-08, 公開日: 2015-03-04, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.25 Å)