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==Structure of GS-TnrA complex==
==Structure of GS-TnrA complex==
<StructureSection load='4s0r' size='340' side='right' caption='[[4s0r]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
<StructureSection load='4s0r' size='340' side='right'caption='[[4s0r]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4s0r]] is a 28 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S0R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S0R FirstGlance]. <br>
<table><tr><td colspan='2'>[[4s0r]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S0R FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamate--ammonia_ligase Glutamate--ammonia ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.1.2 6.3.1.2] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4s0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4s0r RCSB], [http://www.ebi.ac.uk/pdbsum/4s0r PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4s0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s0r OCA], [https://pdbe.org/4s0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s0r RCSB], [https://www.ebi.ac.uk/pdbsum/4s0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s0r ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/GLN1A_BACSU GLN1A_BACSU] Glutamine synthetase (GS) is an unusual multitasking protein that functions as an enzyme, a transcription coregulator, and a chaperone in ammonium assimilation and in the regulation of genes involved in nitrogen metabolism (PubMed:25691471). It catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia (PubMed:24158439). Feedback-inhibited GlnA interacts with and regulates the activity of the transcriptional regulator TnrA (PubMed:11719184, PubMed:12139611). During nitrogen limitation, TnrA is in its DNA-binding active state and turns on the transcription of genes required for nitrogen assimilation (PubMed:11719184, PubMed:12139611, PubMed:25691471). Under conditions of nitrogen excess, feedback-inhibited GlnA forms a stable complex with TnrA, which inhibits its DNA-binding activity (PubMed:11719184, PubMed:12139611, PubMed:25691471). In contrast, feedback-inhibited GlnA acts as a chaperone to stabilize the DNA-binding activity of GlnR, which represses the transcription of nitrogen assimilation genes (PubMed:25691471).<ref>PMID:11719184</ref> <ref>PMID:12139611</ref> <ref>PMID:24158439</ref> <ref>PMID:25691471</ref>  
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.
 
Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis.,Schumacher MA, Chinnam NB, Cuthbert B, Tonthat NK, Whitfill T Genes Dev. 2015 Feb 15;29(4):451-64. doi: 10.1101/gad.254714.114. PMID:25691471<ref>PMID:25691471</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Glutamine synthetase 3D structures|Glutamine synthetase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Glutamate--ammonia ligase]]
[[Category: Bacillus subtilis subsp. subtilis str. 168]]
[[Category: Chinnam, N G]]
[[Category: Large Structures]]
[[Category: Cuthbert, B]]
[[Category: Chinnam NG]]
[[Category: Schumacher, M A]]
[[Category: Cuthbert B]]
[[Category: Tonthat, N K]]
[[Category: Schumacher MA]]
[[Category: Chaperone]]
[[Category: Tonthat NK]]
[[Category: Glutamine synthesis]]
[[Category: Ligase]]
[[Category: Transcription regulation]]

Latest revision as of 15:57, 1 March 2024

Structure of GS-TnrA complexStructure of GS-TnrA complex

Structural highlights

4s0r is a 28 chain structure with sequence from Bacillus subtilis subsp. subtilis str. 168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.5Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLN1A_BACSU Glutamine synthetase (GS) is an unusual multitasking protein that functions as an enzyme, a transcription coregulator, and a chaperone in ammonium assimilation and in the regulation of genes involved in nitrogen metabolism (PubMed:25691471). It catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia (PubMed:24158439). Feedback-inhibited GlnA interacts with and regulates the activity of the transcriptional regulator TnrA (PubMed:11719184, PubMed:12139611). During nitrogen limitation, TnrA is in its DNA-binding active state and turns on the transcription of genes required for nitrogen assimilation (PubMed:11719184, PubMed:12139611, PubMed:25691471). Under conditions of nitrogen excess, feedback-inhibited GlnA forms a stable complex with TnrA, which inhibits its DNA-binding activity (PubMed:11719184, PubMed:12139611, PubMed:25691471). In contrast, feedback-inhibited GlnA acts as a chaperone to stabilize the DNA-binding activity of GlnR, which represses the transcription of nitrogen assimilation genes (PubMed:25691471).[1] [2] [3] [4]

See Also

References

  1. ↑ Wray LV Jr, Zalieckas JM, Fisher SH. Bacillus subtilis glutamine synthetase controls gene expression through a protein-protein interaction with transcription factor TnrA. Cell. 2001 Nov 16;107(4):427-35. PMID:11719184
  2. ↑ Fisher SH, Brandenburg JL, Wray LV Jr. Mutations in Bacillus subtilis glutamine synthetase that block its interaction with transcription factor TnrA. Mol Microbiol. 2002 Aug;45(3):627-35. doi: 10.1046/j.1365-2958.2002.03054.x. PMID:12139611 doi:http://dx.doi.org/10.1046/j.1365-2958.2002.03054.x
  3. ↑ Murray DS, Chinnam N, Tonthat NK, Whitfill T, Wray LV, Fisher SH, Schumacher MA. Structures of the B. subtilis glutamine synthetase dodecamer reveal large intersubunit catalytic conformational changes linked to a unique feedback inhibition mechanism. J Biol Chem. 2013 Oct 24. PMID:24158439 doi:http://dx.doi.org/10.1074/jbc.M113.519496
  4. ↑ Schumacher MA, Chinnam NB, Cuthbert B, Tonthat NK, Whitfill T. Structures of regulatory machinery reveal novel molecular mechanisms controlling B. subtilis nitrogen homeostasis. Genes Dev. 2015 Feb 15;29(4):451-64. doi: 10.1101/gad.254714.114. PMID:25691471 doi:http://dx.doi.org/10.1101/gad.254714.114

4s0r, resolution 3.50Å

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