5ext
From Proteopedia
AAA+ domain of FleQ from Pseudomonas aeruginosa bound to ADP
Structural highlights
FunctionFLEQ_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 PubMedBacterial 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
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