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| | ==Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain-DNA Complex== | | ==Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain-DNA Complex== |
| - | <StructureSection load='1zlk' size='340' side='right' caption='[[1zlk]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='1zlk' size='340' side='right'caption='[[1zlk]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zlk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZLK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZLK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zlk]] 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=1ZLK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZLK FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zlj|1zlj]]</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]] 3.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dosR, devR, Rv3133c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=1zlk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlk OCA], [https://pdbe.org/1zlk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zlk RCSB], [https://www.ebi.ac.uk/pdbsum/1zlk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zlk ProSAT], [https://www.topsan.org/Proteins/TBSGC/1zlk TOPSAN]</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=1zlk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlk OCA], [http://pdbe.org/1zlk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zlk RCSB], [http://www.ebi.ac.uk/pdbsum/1zlk PDBsum], [http://www.topsan.org/Proteins/TBSGC/1zlk TOPSAN]</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/zl/1zlk_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zl/1zlk_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> |
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| | ==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: Hol, W G.J]] | + | [[Category: Large Structures]] |
| - | [[Category: Rice, A E]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Roberts, D M]] | + | [[Category: Hol WGJ]] |
| - | [[Category: Sherman, D R]] | + | [[Category: Rice AE]] |
| - | [[Category: Wisedchaisri, G]] | + | [[Category: Roberts DM]] |
| - | [[Category: Wu, M]] | + | [[Category: Sherman DR]] |
| - | [[Category: Helix-turn-helix]] | + | [[Category: Wisedchaisri G]] |
| - | [[Category: Protein-dna complex]] | + | [[Category: Wu M]] |
| - | [[Category: Transcription-dna complex]]
| + | |
| 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
On encountering low oxygen conditions, DosR activates the transcription of 47 genes, promoting long-term survival of Mycobacterium tuberculosis in a non-replicating state. Here, we report the crystal structures of the DosR C-terminal domain and its complex with a consensus DNA sequence of the hypoxia-induced gene promoter. The DosR C-terminal domain contains four alpha-helices and forms tetramers consisting of two dimers with non-intersecting dyads. In the DNA-bound structure, each DosR C-terminal domain in a dimer places its DNA-binding helix deep into the major groove, causing two bends in the DNA. DosR makes numerous protein-DNA base contacts using only three amino acid residues per subunit: Lys179, Lys182, and Asn183. The DosR tetramer is unique among response regulators with known structures.
Structures of Mycobacterium tuberculosis DosR and DosR-DNA complex involved in gene activation during adaptation to hypoxic latency.,Wisedchaisri G, Wu M, Rice AE, Roberts DM, Sherman DR, Hol WG J Mol Biol. 2005 Dec 2;354(3):630-41. Epub 2005 Oct 3. PMID:16246368[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, Rice AE, Roberts DM, Sherman DR, Hol WG. Structures of Mycobacterium tuberculosis DosR and DosR-DNA complex involved in gene activation during adaptation to hypoxic latency. J Mol Biol. 2005 Dec 2;354(3):630-41. Epub 2005 Oct 3. PMID:16246368 doi:10.1016/j.jmb.2005.09.048
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