Structure-based molecular characterization of the YetL transcription factor from Bacillus subtilis

Abstract

Bacillus subtilis is a gram-positive bacterium that has developed to coordinate gene expression and to survive against changes of nutrients and toxic chemicals. Flavonoids are exuded by plant cells and are abundant in the soil. To counteract the antibacterial effects of flavonoids, B. subtilis expresses flavonoid-detoxifying enzymes, and their expression is negatively regulated by transcription factors, including YetL. YetL was shown to control B. subtilis growth through the promoter regions of yetL and yetM genes in response to some flavonoids. Despite the functional significance of the YetL transcription factor in bacterial survival, no structural information is available for YetL. Here, we report the crystal structure of YetL and propose a flavonoid-induced regulatory mechanism. The YetL structure contains the canonical winged helix-turn-helix motif of the MarR superfamily but distinctly presents an additional N-terminal helix. In the dimeric assembly of YetL, the H1 helix intersects the YetL dimer and contributes to extensive intersubunit interactions. As a transcription factor, YetL recognizes a 28-mer operator of double-stranded DNA that contains a palindromic sequence. Moreover, our comparative structural analysis of YetL and other MarR members allows us to propose a flavonoid-induced transcription regulatory mechanism that is used for bacterial adaptation to environmental changes and stresses.