Structural basis for DNA recognition by the transcription regulator MetR

摘要: MetR, a LysR-type transcriptional regulator (LTTR), has been extensively studied owing to its role in the control of methionine biosynthesis proteobacteria. A MetR homodimer binds 24-base-pair operator region met genes and specifically recognizes interrupted palindromic sequence 5′-TGAA-N5-TTCA-3′. Mechanistic details underlying interaction with target DNA at molecular level remain unknown. In this work, crystal structure DNA-binding domain (DBD) was determined 2.16 A resolution. MetR-DBD adopts winged-helix–turn–helix (wHTH) motif shares significant fold similarity DBD LTTR protein BenM. Furthermore, data-driven macromolecular-docking strategy used model bound DNA, which revealed that bent conformation is required for recognition helix α3 wing loop wHTH interact major minor grooves, respectively. Comparison MetR-DBD–DNA complex structures other LTTR-DBD–DNA complexes residues may confer operator-sequence binding specificity MetR. Taken together, results show uses combination direct base-specific interactions indirect shape promoter regulate transcription genes.