Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis

Schumacher, Maria A.; Chinnam, Naga babu; Cuthbert, Bonnie; Tonthat, Nam K.; Whitfill, Travis

doi:10.1101/gad.254714.114

Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis

Journal Article · Sun Feb 15 00:00:00 EST 2015 · Genes & Development

DOI:https://doi.org/10.1101/gad.254714.114· OSTI ID:1625613

Schumacher, Maria A. ^[1]; Chinnam, Naga babu ^[2]; Cuthbert, Bonnie ^[2]; Tonthat, Nam K. ^[2]; Whitfill, Travis ^[2]

Duke Univ., Durham, NC (United States). Medical Center. Dept. of Biochemistry; DOE/OSTI
Duke Univ., Durham, NC (United States). Medical Center. Dept. of Biochemistry

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625613

Journal Information:: Genes & Development, Journal Name: Genes & Development Journal Issue: 4 Vol. 29; ISSN 0890-9369

Publisher:: Cold Springs Harbor Laboratory PressCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis

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