マイコプラズマ・ジェニタリウムにおける細胞分裂調節因子MraZによる転写調節の構造基盤

Cell division is a central process in all living organisms and requires the coordinated action of many proteins and regulatory elements. In most bacteria, the division and cell wall (dcw) gene cluster is regulated by the first gene of the dcw operon, mraZ, a highly conserved DNA-binding transcriptional regulator. Here we report the structural basis of MraZ transcriptional regulation by the resolution of three different cryo-EM structures of MraZ in complex with the upstream promoter region of the dcw cluster from Mycoplasma genitalium at 3.36, 3.57 and 3.87 Å resolution. The structures reveal the specific interactions between MraZ DNA-binding motif and nucleobases of the binding boxes, which induces distortion in the MraZ octamer to enable the interaction with the four repetitive binding boxes of the promoter DNA. The "cradle-like" DNA-binding motif of MraZ exposes three highly conserved basic residues, Lys13, Arg15 and Arg86, which are essential for binding to the consensus sequence of its cognate promoter. Ultimately, the mechanism behind MraZ's DNA binding and regulation of the dcw operon could be translated to other species, working as a general mechanism for the regulation of dcw gene cluster in bacteria.