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| | ==Structure of N-terminal Domain of MtrA== | | ==Structure of N-terminal Domain of MtrA== |
| - | <StructureSection load='3nhz' size='340' side='right' caption='[[3nhz]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3nhz' size='340' side='right'caption='[[3nhz]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nhz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NHZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nhz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NHZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gwr|2gwr]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mtra, TBMG_03294 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</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=3nhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nhz OCA], [https://pdbe.org/3nhz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nhz RCSB], [https://www.ebi.ac.uk/pdbsum/3nhz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nhz ProSAT]</span></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=3nhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nhz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nhz RCSB], [http://www.ebi.ac.uk/pdbsum/3nhz PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MTRA_MYCTU MTRA_MYCTU] Member of the two-component regulatory system MtrA/MtrB. Binds direct repeat motifs of sequence 5'-GTCACAGCG-3', phosphorylation confers higher affinity. Overexpression decreases bacteria viability upon infection of human THP-1 macrophage cell line, due at least in part to impaired blockage of phagosome-lysosome fusion (upon infection bacteria usually remain in phagosomes). Infecting C57BL/6 mice with an overexpressing strain leads to an attentuated infection in both spleen and lungs. The level of dnaA mRNA increases dramatically. Binds the promoter of dnaA, fbpD, ripA and itself, as well as oriC, which it may regulate. Upon co-overexpression of MrtA and MtrB growth in macrophages is partially restored, dnaA expression is not induced, although mouse infections are still attenuated, suggesting that bacterial growth in macrophages requires an optimal ratio of MtrB to MtrA.<ref>PMID:20223818</ref> <ref>PMID:21295603</ref> <ref>PMID:22610443</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nh/3nhz_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nh/3nhz_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3nhz ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3nhz" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Response regulator|Response regulator]] | + | *[[Response regulator 3D structure|Response regulator 3D structure]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Barbieri, C M]] | + | [[Category: Barbieri CM]] |
| - | [[Category: Mack, T R]] | + | [[Category: Mack TR]] |
| - | [[Category: Miller, M T]] | + | [[Category: Miller MT]] |
| - | [[Category: Robinson, V L]] | + | [[Category: Robinson VL]] |
| - | [[Category: Stock, A M]] | + | [[Category: Stock AM]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Two-component regulatory system]]
| + | |
| Structural highlights
Function
MTRA_MYCTU Member of the two-component regulatory system MtrA/MtrB. Binds direct repeat motifs of sequence 5'-GTCACAGCG-3', phosphorylation confers higher affinity. Overexpression decreases bacteria viability upon infection of human THP-1 macrophage cell line, due at least in part to impaired blockage of phagosome-lysosome fusion (upon infection bacteria usually remain in phagosomes). Infecting C57BL/6 mice with an overexpressing strain leads to an attentuated infection in both spleen and lungs. The level of dnaA mRNA increases dramatically. Binds the promoter of dnaA, fbpD, ripA and itself, as well as oriC, which it may regulate. Upon co-overexpression of MrtA and MtrB growth in macrophages is partially restored, dnaA expression is not induced, although mouse infections are still attenuated, suggesting that bacterial growth in macrophages requires an optimal ratio of MtrB to MtrA.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
DNA-binding response regulators of the OmpR/PhoB subfamily alternate between inactive and active conformational states, with the latter having enhanced DNA-binding affinity. Phosphorylation of an aspartate residue in the receiver domain, usually via phosphotransfer from a cognate histidine kinase, stabilizes the active conformation. Many of the available structures of inactive OmpR/PhoB family proteins exhibit extensive interfaces between the N-terminal receiver and C-terminal DNA-binding domains. These interfaces invariably involve the alpha4-beta5-alpha5 face of the receiver domain, the locus of the largest differences between inactive and active conformations and the surface that mediates dimerization of receiver domains in the active state. Structures of receiver domain dimers of DrrB, DrrD and MtrA have been determined and phosphorylation kinetics analyzed. Analysis of phosphotransfer from small molecule phosphodonors has revealed large differences in autophosphorylation rates among OmpR/PhoB response regulators. Response regulators with substantial domain interfaces exhibit slow rates of phosphorylation. Rates are greatly increased in isolated receiver domain constructs. Such differences are not observed between autophosphorylation rates of full-length and isolated receiver domain of a response regulator that lacks interdomain interfaces nor are they observed in histidine kinase-mediated phosphotransfer. These findings suggest that domain interfaces restrict receiver domain conformational dynamics, stabilizing an inactive conformation that is catalytically incompetent for phosphotransfer from small molecule phosphodonors. Inhibition of phosphotransfer by domain interfaces provides an explanation for the observation that some response regulators cannot be phosphorylated by small molecule phosphodonors in vitro and provides a potential mechanism for insulating some response regulators from small molecule-mediated phosphorylation in vivo.
Regulation of response regulator autophosphorylation through interdomain contacts.,Barbieri CM, Mack TR, Robinson VL, Miller MT, Stock AM J Biol Chem. 2010 Aug 11. PMID:20702407[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rajagopalan M, Dziedzic R, Al Zayer M, Stankowska D, Ouimet MC, Bastedo DP, Marczynski GT, Madiraju MV. Mycobacterium tuberculosis origin of replication and the promoter for immunodominant secreted antigen 85B are the targets of MtrA, the essential response regulator. J Biol Chem. 2010 May 21;285(21):15816-27. PMID:20223818 doi:10.1074/jbc.M109.040097
- ↑ Al Zayer M, Stankowska D, Dziedzic R, Sarva K, Madiraju MV, Rajagopalan M. Mycobacterium tuberculosis mtrA merodiploid strains with point mutations in the signal-receiving domain of MtrA exhibit growth defects in nutrient broth. Plasmid. 2011 May;65(3):210-8. PMID:21295603 doi:10.1016/j.plasmid.2011.01.002
- ↑ Plocinska R, Purushotham G, Sarva K, Vadrevu IS, Pandeeti EV, Arora N, Plocinski P, Madiraju MV, Rajagopalan M. Septal localization of the Mycobacterium tuberculosis MtrB sensor kinase promotes MtrA regulon expression. J Biol Chem. 2012 Jul 6;287(28):23887-99. PMID:22610443 doi:10.1074/jbc.M112.346544
- ↑ Barbieri CM, Mack TR, Robinson VL, Miller MT, Stock AM. Regulation of response regulator autophosphorylation through interdomain contacts. J Biol Chem. 2010 Aug 11. PMID:20702407 doi:10.1074/jbc.M110.157164
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