7r3g
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==PROSS optimitzed variant of RhlR (75 mutations) in complex with the synthetic antagonist mBTL== | |
| + | <StructureSection load='7r3g' size='340' side='right'caption='[[7r3g]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7r3g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R3G FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K5G:4-(3-bromophenoxy)-N-[(3S)-2-oxothiolan-3-yl]butanamide'>K5G</scene></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=7r3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r3g OCA], [https://pdbe.org/7r3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r3g RCSB], [https://www.ebi.ac.uk/pdbsum/7r3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r3g ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RHLR_PSEAE RHLR_PSEAE] Quorum-sensing regulator that controls the expression of multiple virulence factors in response to extracellular signaling molecules called autoinducers (PubMed:7494482, PubMed:8522523, PubMed:15576196). Involved, among others, in the transcriptional regulation of genes that are responsible for rhamnolipid surfactant biosynthesis (PubMed:8144472, PubMed:7604006, PubMed:14526008). Acts by binding to a specific sequence in the rhlAB regulatory region, both in the presence and in the absence of its autoinducer (PubMed:14526008). In the former case it activates transcription of the promoter, whereas in the latter it acts as a transcriptional repressor (PubMed:14526008). Also regulates the expression of the rmlBDAC operon, encoding dTDP-L-rhamnose biosynthetic enzymes, by binding to the rml box in the promoter region (PubMed:22262098). In addition, is involved in the regulation of the production of elastase (lasB) and pyocyanine (PubMed:8144472, PubMed:7604006, PubMed:8522523).<ref>PMID:14526008</ref> <ref>PMID:15576196</ref> <ref>PMID:22262098</ref> <ref>PMID:7494482</ref> <ref>PMID:7604006</ref> <ref>PMID:8144472</ref> <ref>PMID:8522523</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Pseudomonas aeruginosa is a major cause of nosocomial infections and also leads to severe exacerbations in cystic fibrosis or chronic obstructive pulmonary disease. Three intertwined quorum sensing systems control virulence of P. aeruginosa, with the rhl circuit playing the leading role in late and chronic infections. The majority of traits controlled by rhl transcription factor RhlR depend on PqsE, a dispensable thioesterase in Pseudomonas Quinolone Signal (PQS) biosynthesis that interferes with RhlR through an enigmatic mechanism likely involving direct interaction of both proteins. Here we show that PqsE and RhlR form a 2:2 protein complex that, together with RhlR agonist N-butanoyl-L-homoserine lactone (C4-HSL), solubilizes RhlR and thereby renders the otherwise insoluble transcription factor active. We determine crystal structures of the complex and identify residues essential for the interaction. To corroborate the chaperone-like activity of PqsE, we design stability-optimized variants of RhlR that bypass the need for C4-HSL and PqsE in activating PqsE/RhlR-controlled processes of P. aeruginosa. Together, our data provide insight into the unique regulatory role of PqsE and lay groundwork for developing new P. aeruginosa-specific pharmaceuticals. | ||
| - | + | Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa.,Borgert SR, Henke S, Witzgall F, Schmelz S, Zur Lage S, Hotop SK, Stephen S, Lubken D, Kruger J, Gomez NO, van Ham M, Jansch L, Kalesse M, Pich A, Bronstrup M, Haussler S, Blankenfeldt W Nat Commun. 2022 Dec 1;13(1):7402. doi: 10.1038/s41467-022-35030-w. PMID:36456567<ref>PMID:36456567</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7r3g" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pseudomonas aeruginosa PAO1]] | ||
| + | [[Category: Blankenfeldt W]] | ||
| + | [[Category: Henke S]] | ||
Revision as of 09:59, 14 December 2022
PROSS optimitzed variant of RhlR (75 mutations) in complex with the synthetic antagonist mBTL
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