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| | ==Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain Crystal Form II== | | ==Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain Crystal Form II== |
| - | <StructureSection load='3c57' size='340' side='right' caption='[[3c57]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='3c57' size='340' side='right'caption='[[3c57]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3c57]] is a 2 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=3C57 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3C57 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3c57]] is a 2 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=3C57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C57 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c3w|3c3w]], [[1zlj|1zlj]], [[1zlk|1zlk]]</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]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">devR ([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=3c57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c57 OCA], [https://pdbe.org/3c57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c57 RCSB], [https://www.ebi.ac.uk/pdbsum/3c57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c57 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=3c57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c57 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3c57 RCSB], [http://www.ebi.ac.uk/pdbsum/3c57 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DEVR_MYCTU DEVR_MYCTU] Member of the two-component regulatory system DevR/DevS (also called DosR/DosS) involved in onset of the dormancy response (PubMed:15033981). Regulates an approximately 48-member regulon (PubMed:12953092, PubMed:11416222, PubMed:15033981, PubMed:18400743). When phosphorylated binds and activates the promoter of DevR regulon genes in response to hypoxia (PubMed:18359816, PubMed:21764934, PubMed:28977726). The presence of target DNA increases stability of phospho-DevR in vitro (PubMed:28977726). Activates its own transcription under hypoxic but not aerobic conditions, probably binds as a dimer to tandem binding sites within the devR and hspX promoters (PubMed:18359816). Accepts a phosphate group from DevS (DosS) and from DosT (PubMed:15033981, PubMed:15073296, PubMed:21764934, PubMed:28977726). Does not regulate transcription of dosT (PubMed:19487478).<ref>PMID:11416222</ref> <ref>PMID:12953092</ref> <ref>PMID:15033981</ref> <ref>PMID:15073296</ref> <ref>PMID:18359816</ref> <ref>PMID:18400743</ref> <ref>PMID:19487478</ref> <ref>PMID:21764934</ref> <ref>PMID:28977726</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/c5/3c57_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c5/3c57_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=3c57 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 3c57" 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: Hol, W G.J]] | + | [[Category: Hol WGJ]] |
| - | [[Category: Sherman, D R]] | + | [[Category: Sherman DR]] |
| - | [[Category: Wisedchaisri, G]] | + | [[Category: Wisedchaisri G]] |
| - | [[Category: Wu, M]] | + | [[Category: Wu M]] |
| - | [[Category: Dna-binding protein]]
| + | |
| - | [[Category: Response regulator]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Tuberculosis]]
| + | |
| - | [[Category: Two-component regulatory system]]
| + | |
| Structural highlights
Function
DEVR_MYCTU Member of the two-component regulatory system DevR/DevS (also called DosR/DosS) involved in onset of the dormancy response (PubMed:15033981). Regulates an approximately 48-member regulon (PubMed:12953092, PubMed:11416222, PubMed:15033981, PubMed:18400743). When phosphorylated binds and activates the promoter of DevR regulon genes in response to hypoxia (PubMed:18359816, PubMed:21764934, PubMed:28977726). The presence of target DNA increases stability of phospho-DevR in vitro (PubMed:28977726). Activates its own transcription under hypoxic but not aerobic conditions, probably binds as a dimer to tandem binding sites within the devR and hspX promoters (PubMed:18359816). Accepts a phosphate group from DevS (DosS) and from DosT (PubMed:15033981, PubMed:15073296, PubMed:21764934, PubMed:28977726). Does not regulate transcription of dosT (PubMed:19487478).[1] [2] [3] [4] [5] [6] [7] [8] [9]
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
The response regulator DosR is essential for promoting long-term survival of Mycobacterium tuberculosis under low oxygen conditions in a dormant state and may be responsible for latent tuberculosis in one-third of the world's population. Here, we report crystal structures of full-length unphosphorylated DosR at 2.2 A resolution and its C-terminal DNA-binding domain at 1.7 A resolution. The full-length DosR structure reveals several features never seen before in other response regulators. The N-terminal domain of the full-length DosR structure has an unexpected (beta alpha)(4) topology instead of the canonical (beta alpha)(5) fold observed in other response regulators. The linker region adopts a unique conformation that contains two helices forming a four-helix bundle with two helices from another subunit, resulting in dimer formation. The C-terminal domain in the full-length DosR structure displays a novel location of helix alpha 10, which allows Gln199 to interact with the catalytic Asp54 residue of the N-terminal domain. In contrast, the structure of the DosR C-terminal domain alone displays a remarkable unstructured conformation for helix alpha 10 residues, different from the well-defined helical conformations in all other known structures, indicating considerable flexibility within the C-terminal domain. Our structures suggest a mode of DosR activation by phosphorylation via a helix rearrangement mechanism.
Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation.,Wisedchaisri G, Wu M, Sherman DR, Hol WG J Mol Biol. 2008 Apr 18;378(1):227-42. Epub 2008 Feb 26. PMID:18353359[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sherman DR, Voskuil M, Schnappinger D, Liao R, Harrell MI, Schoolnik GK. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7534-9. PMID:11416222 doi:10.1073/pnas.121172498
- ↑ Voskuil MI, Schnappinger D, Visconti KC, Harrell MI, Dolganov GM, Sherman DR, Schoolnik GK. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med. 2003 Sep 1;198(5):705-13. PMID:12953092 doi:10.1084/jem.20030205
- ↑ Roberts DM, Liao RP, Wisedchaisri G, Hol WG, Sherman DR. Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis. J Biol Chem. 2004 May 28;279(22):23082-7. Epub 2004 Mar 19. PMID:15033981 doi:10.1074/jbc.M401230200
- ↑ Saini DK, Malhotra V, Dey D, Pant N, Das TK, Tyagi JS. DevR-DevS is a bona fide two-component system of Mycobacterium tuberculosis that is hypoxia-responsive in the absence of the DNA-binding domain of DevR. Microbiology (Reading). 2004 Apr;150(Pt 4):865-875. PMID:15073296 doi:10.1099/mic.0.26218-0
- ↑ Chauhan S, Tyagi JS. Cooperative binding of phosphorylated DevR to upstream sites is necessary and sufficient for activation of the Rv3134c-devRS operon in Mycobacterium tuberculosis: implication in the induction of DevR target genes. J Bacteriol. 2008 Jun;190(12):4301-12. PMID:18359816 doi:10.1128/JB.01308-07
- ↑ Kumar A, Deshane JS, Crossman DK, Bolisetty S, Yan BS, Kramnik I, Agarwal A, Steyn AJ. Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon. J Biol Chem. 2008 Jun 27;283(26):18032-9. doi: 10.1074/jbc.M802274200. Epub 2008 , Apr 9. PMID:18400743 doi:10.1074/jbc.M802274200
- ↑ Honaker RW, Leistikow RL, Bartek IL, Voskuil MI. Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium tuberculosis dormancy. Infect Immun. 2009 Aug;77(8):3258-63. PMID:19487478 doi:10.1128/IAI.01449-08
- ↑ Gautam US, Sikri K, Tyagi JS. The residue threonine 82 of DevR (DosR) is essential for DevR activation and function in Mycobacterium tuberculosis despite its atypical location. J Bacteriol. 2011 Sep;193(18):4849-58. PMID:21764934 doi:10.1128/JB.05051-11
- ↑ Sousa EHS, Gonzalez G, Gilles-Gonzalez MA. Target DNA stabilizes Mycobacterium tuberculosis DevR/DosR phosphorylation by the full-length oxygen sensors DevS/DosS and DosT. FEBS J. 2017 Nov;284(22):3954-3967. PMID:28977726 doi:10.1111/febs.14284
- ↑ Wisedchaisri G, Wu M, Sherman DR, Hol WG. Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation. J Mol Biol. 2008 Apr 18;378(1):227-42. Epub 2008 Feb 26. PMID:18353359 doi:10.1016/j.jmb.2008.02.029
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