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| | ==Crystal structure of Repressor of Toxin (Rot), a central regulator of Staphylococcus aureus virulence== | | ==Crystal structure of Repressor of Toxin (Rot), a central regulator of Staphylococcus aureus virulence== |
| - | <StructureSection load='4rbr' size='340' side='right' caption='[[4rbr]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4rbr' size='340' side='right'caption='[[4rbr]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rbr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_cn1 Staphylococcus aureus subsp. aureus cn1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RBR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RBR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rbr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_CN1 Staphylococcus aureus subsp. aureus CN1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RBR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RBR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SAKOR_01705 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1193576 Staphylococcus aureus subsp. aureus CN1])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=4rbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rbr OCA], [http://pdbe.org/4rbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rbr RCSB], [http://www.ebi.ac.uk/pdbsum/4rbr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rbr 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=4rbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rbr OCA], [https://pdbe.org/4rbr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rbr RCSB], [https://www.ebi.ac.uk/pdbsum/4rbr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rbr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/T1YAC1_STAAU T1YAC1_STAAU]] Global regulator with both positive and negative effects that mediates modulation of several genes involved in virulence.[PIRNR:PIRNR032474] | + | [https://www.uniprot.org/uniprot/T1YAC1_STAAU T1YAC1_STAAU] Global regulator with both positive and negative effects that mediates modulation of several genes involved in virulence.[PIRNR:PIRNR032474] |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Staphylococcus aureus is responsible for a large number of diverse infections worldwide. In order to support its pathogenic lifestyle, S. aureus has to regulate the expression of virulence factors in a coordinated fashion. One of the central regulators of the S. aureus virulence regulatory networks is the transcription factor Repressor of Toxins (Rot). Rot plays a key role in regulating S. aureus virulence through activation or repression of promoters that control expression of a large number of critical virulence factors. However, the mechanism by which Rot-mediates gene regulation has remained elusive. Here, we have we determined the crystal structure of Rot and used this information to probe the contribution made by specific residues to Rot function. Rot was found to form a dimer, with each monomer harboring a Winged-Helix-Turn-Helix (WHTH) DNA binding motif. Despite an overall acidic pI, the asymmetric electrostatic charge profile suggests that Rot can orient the WHTH domain to bind DNA. Structure-based site-directed mutagenesis studies demonstrated that R91, at the tip of the wing, plays an important role in DNA-binding, likely through interaction with the minor groove. We also found that Y66, predicted to bind within the major groove, contributes to Rot interaction with target promoters. Evaluation of Rot binding to different activated and repressed promoters revealed that certain mutations on Rot exhibit promoter-specific effects, suggesting for the first time that Rot differentially interacts with target promoters. This work provides insight into a precise mechanism by which Rot controls virulence factor regulation in S. aureus.
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| - | Structure-based functional characterization of Repressor of Toxin (Rot), a central regulator of Staphylococcus aureus virulence.,Killikelly A, Benson MA, Ohneck EA, Sampson JM, Jakoncic J, Spurrier B, Torres VJ, Kong XP J Bacteriol. 2014 Oct 20. pii: JB.02317-14. PMID:25331435<ref>PMID:25331435</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4rbr" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Staphylococcus aureus subsp. aureus cn1]] | + | [[Category: Large Structures]] |
| - | [[Category: Jakoncic, J]] | + | [[Category: Staphylococcus aureus subsp. aureus CN1]] |
| - | [[Category: Killikelly, A]] | + | [[Category: Jakoncic J]] |
| - | [[Category: Kong, X P]] | + | [[Category: Killikelly A]] |
| - | [[Category: Sampson, J M]] | + | [[Category: Kong X-P]] |
| - | [[Category: Dna binding]]
| + | [[Category: Sampson JM]] |
| - | [[Category: Dna binding protein]]
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| - | [[Category: Virulence regulator]]
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| - | [[Category: Winged-helix-turn-helix]]
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