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| | <StructureSection load='5exp' size='340' side='right'caption='[[5exp]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='5exp' size='340' side='right'caption='[[5exp]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5exp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EXP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5exp]] is a 1 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=5EXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EXP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5exs|5exs]], [[5ext|5ext]], [[5exx|5exx]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fleQ, PA1097 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</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=5exp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exp OCA], [https://pdbe.org/5exp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5exp RCSB], [https://www.ebi.ac.uk/pdbsum/5exp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5exp ProSAT]</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=5exp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exp OCA], [http://pdbe.org/5exp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exp RCSB], [http://www.ebi.ac.uk/pdbsum/5exp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5exp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FLEQ_PSEAE FLEQ_PSEAE] AAA+ ATPase enhancer-binding protein that acts as a transcription regulator and plays a role in the modulation of mucin adhesion and flagellar gene expression (PubMed:9287015, PubMed:11673434, PubMed:26362077). In addition to flagella genes, regulates also expression of biofilm-related genes (PubMed:22581773). Functions as a transcriptional repressor in the absence of c-di-GMP and as an activator when c-di-GMP is present (PubMed:22581773).<ref>PMID:11673434</ref> <ref>PMID:22581773</ref> <ref>PMID:26362077</ref> <ref>PMID:9287015</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pseae]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Matsuyama, B Y]] | + | [[Category: Matsuyama BY]] |
| - | [[Category: Navarro, M V.A S]] | + | [[Category: Navarro MVAS]] |
| - | [[Category: Sondermann, H]] | + | [[Category: Sondermann H]] |
| - | [[Category: Aaa+]]
| + | |
| - | [[Category: Atpase]]
| + | |
| - | [[Category: C-di-gmp]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Function
FLEQ_PSEAE AAA+ ATPase enhancer-binding protein that acts as a transcription regulator and plays a role in the modulation of mucin adhesion and flagellar gene expression (PubMed:9287015, PubMed:11673434, PubMed:26362077). In addition to flagella genes, regulates also expression of biofilm-related genes (PubMed:22581773). Functions as a transcriptional repressor in the absence of c-di-GMP and as an activator when c-di-GMP is present (PubMed:22581773).[1] [2] [3] [4]
Publication Abstract from PubMed
Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase sigma54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ's AAA+ ATPase domain in its apo-state or bound to ADP or ATP-gamma-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP-complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.
Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa.,Matsuyama BY, Krasteva PV, Baraquet C, Harwood CS, Sondermann H, Navarro MV Proc Natl Acad Sci U S A. 2015 Dec 28. pii: 201523148. PMID:26712005[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dasgupta N, Ramphal R. Interaction of the antiactivator FleN with the transcriptional activator FleQ regulates flagellar number in Pseudomonas aeruginosa. J Bacteriol. 2001 Nov;183(22):6636-44. PMID:11673434 doi:10.1128/JB.183.22.6636-6644.2001
- ↑ Baraquet C, Murakami K, Parsek MR, Harwood CS. The FleQ protein from Pseudomonas aeruginosa functions as both a repressor and an activator to control gene expression from the pel operon promoter in response to c-di-GMP. Nucleic Acids Res. 2012 Aug;40(15):7207-18. PMID:22581773 doi:10.1093/nar/gks384
- ↑ Su T, Liu S, Wang K, Chi K, Zhu D, Wei T, Huang Y, Guo L, Hu W, Xu S, Lin Z, Gu L. The REC domain mediated dimerization is critical for FleQ from Pseudomonas aeruginosa to function as a c-di-GMP receptor and flagella gene regulator. J Struct Biol. 2015 Oct;192(1):1-13. doi: 10.1016/j.jsb.2015.09.002. Epub 2015, Sep 8. PMID:26362077 doi:http://dx.doi.org/10.1016/j.jsb.2015.09.002
- ↑ Arora SK, Ritchings BW, Almira EC, Lory S, Ramphal R. A transcriptional activator, FleQ, regulates mucin adhesion and flagellar gene expression in Pseudomonas aeruginosa in a cascade manner. J Bacteriol. 1997 Sep;179(17):5574-81. PMID:9287015 doi:10.1128/jb.179.17.5574-5581.1997
- ↑ Matsuyama BY, Krasteva PV, Baraquet C, Harwood CS, Sondermann H, Navarro MV. Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2015 Dec 28. pii: 201523148. PMID:26712005 doi:http://dx.doi.org/10.1073/pnas.1523148113
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