Cyclic diguanosine monophosphate represses bacterial flagella synthesis by interacting with the Walker A motif of the enhancer-binding protein FleQ

• DOI: 10.1073/pnas.1318972110
• Publication Date: 2013-10-29T03:37:12Z
• Authors: Claudine Baraquet; Caroline S. Harwood
• Keywords: 0301 basic medicine; Amino Acid Motifs; Gene Expression Regulation, Bacterial; 03 medical and health sciences; Bacterial Proteins; Flagella; Mutagenesis; Pseudomonas aeruginosa; Chromatography, Gel; Trans-Activators; Electrophoresis, Polyacrylamide Gel; Cyclic GMP

SignificanceMany bacteria respond to environmental cues by producing cyclic diguanosine monophosphate (c-di-GMP), which binds to proteins to modulate transitions between sessile and motile lifestyles important for chronic and acute infections, respectively. The breadth of protein targets and mechanisms of action of c-di-GMP remain unknown. In the opportunistic pathogenPseudomonas aeruginosa, c-di-GMP binds to FleQ, a transcription factor that is the master regulator of flagella synthesis and a member of the large family of AAA+ ATPase proteins. We found that c-di-GMP competitively inhibits FleQ ATPase activity and interacts with the ATP-binding site on FleQ. We suggest that AAA+ ATPases from other bacteria may respond to c-di-GMP, and that interference with ATPase activity is one mechanism of c-di-GMP action.