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| | ==Crystal structure of EspR transcription factor from mycobacterium tuberculosis== | | ==Crystal structure of EspR transcription factor from mycobacterium tuberculosis== |
| - | <StructureSection load='3qf3' size='340' side='right' caption='[[3qf3]], [[Resolution|resolution]] 2.41Å' scene=''> | + | <StructureSection load='3qf3' size='340' side='right'caption='[[3qf3]], [[Resolution|resolution]] 2.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qf3]] is a 6 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=3QF3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QF3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qf3]] is a 6 chain structure with sequence from [https://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=3QF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QF3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMR:(2S)-2-HYDROXYBUTANEDIOIC+ACID'>LMR</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qwg|3qwg]], [[3qyx|3qyx]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qwg|3qwg]], [[3qyx|3qyx]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">espR, MT3964, Rv3849 ([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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">espR, MT3964, Rv3849 ([https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qf3 OCA], [http://pdbe.org/3qf3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qf3 RCSB], [http://www.ebi.ac.uk/pdbsum/3qf3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qf3 ProSAT]</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=3qf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qf3 OCA], [https://pdbe.org/3qf3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qf3 RCSB], [https://www.ebi.ac.uk/pdbsum/3qf3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qf3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ESPR_MYCTU ESPR_MYCTU]] Virulence regulator that has both architectural and regulatory roles. Impacts cell wall functions and pathogenesis through regulation of multiple genes, including the espACD operon, which is a key ESX-1 component. Influences target gene expression positively or negatively, depending on its binding position relative to the genes it controls. Acts by binding directly to the DNA. May play a central role in regulating virulence gene expression.<ref>PMID:18685700</ref> <ref>PMID:22389481</ref> <ref>PMID:22479184</ref> <ref>PMID:21883526</ref> | + | [[https://www.uniprot.org/uniprot/ESPR_MYCTU ESPR_MYCTU]] Virulence regulator that has both architectural and regulatory roles. Impacts cell wall functions and pathogenesis through regulation of multiple genes, including the espACD operon, which is a key ESX-1 component. Influences target gene expression positively or negatively, depending on its binding position relative to the genes it controls. Acts by binding directly to the DNA. May play a central role in regulating virulence gene expression.<ref>PMID:18685700</ref> <ref>PMID:22389481</ref> <ref>PMID:22479184</ref> <ref>PMID:21883526</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Blasco, B]] | | [[Category: Blasco, B]] |
| | [[Category: Cole, S T]] | | [[Category: Cole, S T]] |
| Structural highlights
Function
[ESPR_MYCTU] Virulence regulator that has both architectural and regulatory roles. Impacts cell wall functions and pathogenesis through regulation of multiple genes, including the espACD operon, which is a key ESX-1 component. Influences target gene expression positively or negatively, depending on its binding position relative to the genes it controls. Acts by binding directly to the DNA. May play a central role in regulating virulence gene expression.[1] [2] [3] [4]
Publication Abstract from PubMed
The human pathogen Mycobacterium tuberculosis requires the ESX-1 secretion system for full virulence. EspR plays a key role in ESX-1 regulation via direct binding and transcriptional activation of the espACD operon. Here, we describe the crystal structures of EspR, a C-terminally truncated form, EspRDelta10, as well as an EspR-DNA complex. EspR forms a dimer with each monomer containing an N-terminal helix-turn-helix DNA binding motif and an atypical C-terminal dimerization domain. Structural studies combined with footprinting experiments, atomic force microscopy and molecular dynamic simulations allow us to propose a model in which a dimer of EspR dimers is the minimal functional unit with two subunits binding two consecutive major grooves. The other two DNA binding domains are thus free to form higher-order oligomers and to bridge distant DNA sites in a cooperative way. These features are reminiscent of nucleoid-associated proteins and suggest a more general regulatory role for EspR than was previously suspected.
Atypical DNA recognition mechanism used by the EspR virulence regulator of Mycobacterium tuberculosis.,Blasco B, Stenta M, Alonso-Sarduy L, Dietler G, Peraro MD, Cole ST, Pojer F Mol Microbiol. 2011 Aug 30. doi: 10.1111/j.1365-2958.2011.07813.x. PMID:21883526[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Raghavan S, Manzanillo P, Chan K, Dovey C, Cox JS. Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature. 2008 Aug 7;454(7205):717-21. doi: 10.1038/nature07219. PMID:18685700 doi:http://dx.doi.org/10.1038/nature07219
- ↑ Hunt DM, Sweeney NP, Mori L, Whalan RH, Comas I, Norman L, Cortes T, Arnvig KB, Davis EO, Stapleton MR, Green J, Buxton RS. Long-range transcriptional control of an operon necessary for virulence-critical ESX-1 secretion in Mycobacterium tuberculosis. J Bacteriol. 2012 May;194(9):2307-20. doi: 10.1128/JB.00142-12. Epub 2012 Mar 2. PMID:22389481 doi:http://dx.doi.org/10.1128/JB.00142-12
- ↑ Blasco B, Chen JM, Hartkoorn R, Sala C, Uplekar S, Rougemont J, Pojer F, Cole ST. Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein. PLoS Pathog. 2012;8(3):e1002621. doi: 10.1371/journal.ppat.1002621. Epub 2012 Mar, 29. PMID:22479184 doi:http://dx.doi.org/10.1371/journal.ppat.1002621
- ↑ Blasco B, Stenta M, Alonso-Sarduy L, Dietler G, Peraro MD, Cole ST, Pojer F. Atypical DNA recognition mechanism used by the EspR virulence regulator of Mycobacterium tuberculosis. Mol Microbiol. 2011 Aug 30. doi: 10.1111/j.1365-2958.2011.07813.x. PMID:21883526 doi:10.1111/j.1365-2958.2011.07813.x
- ↑ Blasco B, Stenta M, Alonso-Sarduy L, Dietler G, Peraro MD, Cole ST, Pojer F. Atypical DNA recognition mechanism used by the EspR virulence regulator of Mycobacterium tuberculosis. Mol Microbiol. 2011 Aug 30. doi: 10.1111/j.1365-2958.2011.07813.x. PMID:21883526 doi:10.1111/j.1365-2958.2011.07813.x
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