|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6onu' size='340' side='right'caption='[[6onu]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='6onu' size='340' side='right'caption='[[6onu]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6onu]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ONU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ONU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6onu]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ONU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ONU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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]] 1.85Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ono|6ono]]</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=6onu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6onu OCA], [https://pdbe.org/6onu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6onu RCSB], [https://www.ebi.ac.uk/pdbsum/6onu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6onu ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">whiB1, Rv3219 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), sigA, mysA, rpoD, rpoV, Rv2703, MTCY05A6.24 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=6onu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6onu OCA], [http://pdbe.org/6onu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6onu RCSB], [http://www.ebi.ac.uk/pdbsum/6onu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6onu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/WHIB1_MYCTU WHIB1_MYCTU]] Acts as a transcriptional repressor, inhibiting expression in vitro. Probably redox-responsive. The apo- but not holo-form binds to its own promoter as well as that of groEL2. Oxidized apo-form and nitrosylated holo-form also bind DNA. The apo-form has been shown to act as a protein disulfide reductase (PubMed:17157031) (PubMed:19016840), but also not to act as a protein disulfide reductase (PubMed:20929442).<ref>PMID:17157031</ref> <ref>PMID:19016840</ref> <ref>PMID:20929442</ref> <ref>PMID:22464736</ref> [[http://www.uniprot.org/uniprot/SIGA_MYCTU SIGA_MYCTU]] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth (Probable).<ref>PMID:12354223</ref> <ref>PMID:20729364</ref> <ref>PMID:22570422</ref> | + | [https://www.uniprot.org/uniprot/WHIB1_MYCTU WHIB1_MYCTU] Acts as a transcriptional repressor, inhibiting expression in vitro. Probably redox-responsive. The apo- but not holo-form binds to its own promoter as well as that of groEL2. Oxidized apo-form and nitrosylated holo-form also bind DNA. The apo-form has been shown to act as a protein disulfide reductase (PubMed:17157031) (PubMed:19016840), but also not to act as a protein disulfide reductase (PubMed:20929442).<ref>PMID:17157031</ref> <ref>PMID:19016840</ref> <ref>PMID:20929442</ref> <ref>PMID:22464736</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6onu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6onu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Sigma factor 3D structures|Sigma factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 26: |
Line 27: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Becker, D C]] | + | [[Category: Becker DC]] |
| - | [[Category: Beltran, D G]] | + | [[Category: Beltran DG]] |
| - | [[Category: Li, S R]] | + | [[Category: Li SR]] |
| - | [[Category: Schacht, A]] | + | [[Category: Schacht A]] |
| - | [[Category: Wan, T]] | + | [[Category: Wan T]] |
| - | [[Category: Zhang, L M]] | + | [[Category: Zhang LM]] |
| - | [[Category: Iron-sulfur cluster]]
| + | |
| - | [[Category: Redox-sensing]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| Structural highlights
Function
WHIB1_MYCTU Acts as a transcriptional repressor, inhibiting expression in vitro. Probably redox-responsive. The apo- but not holo-form binds to its own promoter as well as that of groEL2. Oxidized apo-form and nitrosylated holo-form also bind DNA. The apo-form has been shown to act as a protein disulfide reductase (PubMed:17157031) (PubMed:19016840), but also not to act as a protein disulfide reductase (PubMed:20929442).[1] [2] [3] [4]
Publication Abstract from PubMed
WhiB1 is a monomeric iron-sulfur cluster-containing transcription factor in the WhiB-like family that is widely distributed in actinobacteria including the notoriously persistent pathogen Mycobacterium tuberculosis (M. tuberculosis). WhiB1 plays multiple roles in regulating cell growth and responding to nitric oxide stress in M. tuberculosis, but its underlying mechanism is unclear. Here we report a 1.85 A-resolution crystal structure of the [4Fe-4S] cluster-bound (holo-) WhiB1 in complex with the C-terminal domain of the sigma70-family primary sigma factor sigmaA of M. tuberculosis containing the conserved region 4 (sigmaA4). Region 4 of the sigma70-family primary sigma factors is commonly used by transcription factors for gene activation, and holo-WhiB1 has been proposed to activate gene expression via binding to sigmaA4. The complex structure, however, unexpectedly reveals that the interaction between WhiB1 and sigmaA4 is dominated by hydrophobic residues in the [4Fe-4S] cluster binding pocket, distinct from previously characterized canonical sigma704-bound transcription activators. Furthermore, we show that holo-WhiB1 represses transcription by interaction with sigmaA4in vitro and that WhiB1 must interact with sigmaA4 to perform its essential role in supporting cell growth in vivo. Together, these results demonstrate that holo-WhiB1 regulates gene expression by a non-canonical mechanism relative to well-characterized sigmaA4-dependent transcription activators.
Structural basis of non-canonical transcriptional regulation by the sigmaA-bound iron-sulfur protein WhiB1 in M. tuberculosis.,Wan T, Li S, Beltran DG, Schacht A, Zhang L, Becker DF, Zhang L Nucleic Acids Res. 2019 Dec 6. pii: 5661089. doi: 10.1093/nar/gkz1133. PMID:31807774[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Garg SK, Suhail Alam M, Soni V, Radha Kishan KV, Agrawal P. Characterization of Mycobacterium tuberculosis WhiB1/Rv3219 as a protein disulfide reductase. Protein Expr Purif. 2007 Apr;52(2):422-32. doi: 10.1016/j.pep.2006.10.015. Epub, 2006 Nov 10. PMID:17157031 doi:http://dx.doi.org/10.1016/j.pep.2006.10.015
- ↑ Alam MS, Garg SK, Agrawal P. Studies on structural and functional divergence among seven WhiB proteins of Mycobacterium tuberculosis H37Rv. FEBS J. 2009 Jan;276(1):76-93. doi: 10.1111/j.1742-4658.2008.06755.x. PMID:19016840 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06755.x
- ↑ Smith LJ, Stapleton MR, Fullstone GJ, Crack JC, Thomson AJ, Le Brun NE, Hunt DM, Harvey E, Adinolfi S, Buxton RS, Green J. Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster. Biochem J. 2010 Dec 15;432(3):417-27. PMID:20929442
- ↑ Stapleton MR, Smith LJ, Hunt DM, Buxton RS, Green J. Mycobacterium tuberculosis WhiB1 represses transcription of the essential chaperonin GroEL2. Tuberculosis (Edinb). 2012 Jul;92(4):328-32. doi: 10.1016/j.tube.2012.03.001., Epub 2012 Mar 29. PMID:22464736 doi:http://dx.doi.org/10.1016/j.tube.2012.03.001
- ↑ Wan T, Li S, Beltran DG, Schacht A, Zhang L, Becker DF, Zhang L. Structural basis of non-canonical transcriptional regulation by the sigmaA-bound iron-sulfur protein WhiB1 in M. tuberculosis. Nucleic Acids Res. 2019 Dec 6. pii: 5661089. doi: 10.1093/nar/gkz1133. PMID:31807774 doi:http://dx.doi.org/10.1093/nar/gkz1133
|
