摘要：SummaryThe copper efflux regulator (CueR), a representative member of mercury resistance regulator (MerR) family metalloregulators, controls expression of copper homeostasis-regulating genes in bacteria. The mechanism of transcription activation by CueR and other MerR family regulators is bending the spacer domain of promoter DNA. Here, we report the cryo-EM structures of the intact CueR-dependent transcription activation complexes. The structures show that CueR dimer bends the 19-bp promoter spacer to realign the −35 and −10 elements for recognition by σ70-RNA polymerase holoenzyme and reveal a previously unreported interaction between the DNA-binding domain (DBD) from one CueR subunit and the σ70nonconserved region (σNCR). Functional studies have shown that the CueR-σNCR interaction plays an auxiliary role in CueR-dependent transcription, assisting the activation mechanism of bending promoter DNA by CueR dimer. Because DBDs are highly conserved in sequence and structure, this transcription-activating mechanism could be generally used by MerR family regulators.Graphical abstractDisplay OmittedHighlights•Cryo-EM structures of intact CueR-TAC complex without and with RNA synthesis•CueR dimer activates transcription through bending promoter DNA•The structures reveal the interactions between σNCR and CueR•The σNCR/CueR interactions play an auxiliary role in CueR-dependent transcriptionBiological Sciences; Biochemistry; Structural Biology
