Inactivation of the general transcription factor TnrA in Bacillus subtilis by proteolysis

Kayumov, Airat R.; Heinrich, Annette; Шарипова, М. Р.; Iljinskaya, Olga; Forchhammer, Karl

doi:10.1099/mic.0.2008/019802-0

Cited by 25 publications

(36 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GlnK appears to play an ancillary role in this process by acting as a templating agent for TnrA. This stabilization function is also consistent with data showing that GlnK can protect TnrA against proteolysis (Kayumov et al 2008). In conclusion, our combined data provide detailed molecular snapshots of all of the nitrogen regulatory components and their germane complexes from the model Gram-positive bacteria B. subtilis.…”

Section: Discussionsupporting

confidence: 87%

“…However, when nitrogen is depleted, TnrA is released from GS, activating it for DNA binding. Interestingly, under these conditions, TnrA (but not GlnR) is further stabilized by an interaction with GlnK (Heinrich et al 2006;Kayumov et al 2008Kayumov et al , 2011. The GlnK-and GSinteracting regions in TnrA (residues 75-90 and 95-110, respectively) are highly conserved, while the short region that connects them is not, suggesting that the mechanisms involved in TnrA regulation would be applicable in Bacilli and other Gram-positive bacteria.…”

Section: Regulation Of Glnr Function By Its Nitrogen Sensor Domainmentioning

confidence: 99%

“…Thus, B. subtilis GS is an unusual multitasking protein that functions as an enzyme, transcription coregulator, and chaperone. GlnK appears to play an ancillary role in this pathway during nitrogen depletion by binding and stabilizing TnrA (Heinrich et al 2006;Kayumov et al 2008Kayumov et al , 2011.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Regulation Of Glnr Function By Its Nitrogen Sensor Domainmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…When ATP levels fall in B. subtilis , TnrA, a multivalent transcriptional factor, is sequestered by AmtB–GlnK with presently unknown effects on its transcriptional activity (Heinrich et al ., 2006). Additionally, shifting nitrate‐glucose‐grown cells to nitrogen deprivation leads to release of TnrA from the Amt–PII membrane complex and its subsequent proteolysis (Kayumov et al ., 2008).…”

Section: Sequestration Of Pii Proteins and Regulatory Effectsmentioning

confidence: 99%

Of blood, brains and bacteria, the Amt/Rh transporter family: emerging role of Amt as a unique microbial sensor

Tremblay

Hallenbeck²

2008

Molecular Microbiology

View full text Add to dashboard Cite

SummaryMembers of the Amt/Rh family of transporters are found almost ubiquitously in all forms of life. However, the molecular state of the substrate (NH3 or NH4 + ) has been the subject of active debate. At least for bacterial Amt proteins, the model emerging from computational, X-ray crystal and mutational analysis is that NH4+ is deprotonated at the exterior, conducted through the membrane as NH3, and reprotonated at the cytoplasmic interface. A proton concomitantly is transferred from the exterior to the interior, although the mechanism is unclear. Here we discuss recent evidence indicating that an important function of at least some eukaryotic and bacterial Amts is to act as ammonium sensors and regulate cellular metabolism in response to changes in external ammonium concentrations. This is now well documented in the regulation of yeast pseudohyphal development and filamentous growth. As well, membrane sequestration of GlnK, a PII signal transduction protein, by AmtB has been shown to regulate nitrogenase in some diazotrophs, and nitrogen metabolism in some Gram-positive bacteria. Formation of GlnK-AmtB membrane complexes might have other, as yet undiscovered, regulatory roles. This possibility is emphasized by the discovery in some genomes of genes for chimeric Amts with fusions to various regulatory elements.

show abstract

“…In some cyanobacteria, the LysR family transcription regulator NtcB is required for the nitrate-/nitrite-dependent induction of the nitrate reductase gene [11]. In Gram-positive bacteria such as Bacillus subtilis and Streptomyces coelicolor , the TnrA and GlnR regulators respond to nitrogen starvation [12,13]. In Klebsiella oxytoca , expression of the nitrate assimilation genes is activated under low nitrogen conditions through the global nitrogen regulatory Ntr system, including NtrA, NtrB, and NtrC proteins, and by nitrate/nitrite induction through NasR, a transcription antitermination protein that also binds to nitrate [14,15].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and translational adaptation to aerobic nitrate anabolism in the denitrifier Paracoccus denitrificans

Luque-Almagro

Manso

Sullivan

et al. 2017

Biochemical Journal

View full text Add to dashboard Cite

Transcriptional adaptation to nitrate-dependent anabolism by Paracoccus denitrificans PD1222 was studied. A total of 74 genes were induced in cells grown with nitrate as N-source compared with ammonium, including nasTSABGHC and ntrBC genes. The nasT and nasS genes were cotranscribed, although nasT was more strongly induced by nitrate than nasS. The nasABGHC genes constituted a transcriptional unit, which is preceded by a non-coding region containing hairpin structures involved in transcription termination. The nasTS and nasABGHC transcripts were detected at similar levels with nitrate or glutamate as N-source, but nasABGHC transcript was undetectable in ammonium-grown cells. The nitrite reductase NasG subunit was detected by two-dimensional polyacrylamide gel electrophoresis in cytoplasmic fractions from nitrate-grown cells, but it was not observed when either ammonium or glutamate was used as the N-source. The nasT mutant lacked both nasABGHC transcript and nicotinamide adenine dinucleotide (NADH)-dependent nitrate reductase activity. On the contrary, the nasS mutant showed similar levels of the nasABGHC transcript to the wild-type strain and displayed NasG protein and NADH–nitrate reductase activity with all N-sources tested, except with ammonium. Ammonium repression of nasABGHC was dependent on the Ntr system. The ntrBC and ntrYX genes were expressed at low levels regardless of the nitrogen source supporting growth. Mutational analysis of the ntrBCYX genes indicated that while ntrBC genes are required for nitrate assimilation, ntrYX genes can only partially restore growth on nitrate in the absence of ntrBC genes. The existence of a regulation mechanism for nitrate assimilation in P. denitrificans, by which nitrate induction operates at both transcriptional and translational levels, is proposed.

show abstract

Inactivation of the general transcription factor TnrA in Bacillus subtilis by proteolysis

Cited by 25 publications

References 31 publications

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

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

Of blood, brains and bacteria, the Amt/Rh transporter family: emerging role of Amt as a unique microbial sensor

Transcriptional and translational adaptation to aerobic nitrate anabolism in the denitrifier Paracoccus denitrificans

Contact Info

Product

Resources

About