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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]] 3.50Å' scene=''> | + | <StructureSection load='4s0r' size='340' side='right'caption='[[4s0r]], [[Resolution|resolution]] 3.50Å' 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]] 3.5Å</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.
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| - | 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>
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| - | From MEDLINE®/PubMed®, 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]]
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| - | [[Category: Ligase]]
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| - | [[Category: Transcription regulation]]
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| Structural highlights
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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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