Structural basis of copper-efflux-regulator-dependent transcription activation

Wei Shi, Baoyue Zhang, Yanan Jiang, Chang Liu, Wei Zhou, Ming Chen, Yang Yang, Yangbo Hu, Bin Liu

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5 Scopus citations


The 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 σ70 nonconserved 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.

Original languageEnglish (US)
Article number102449
Issue number5
StatePublished - May 21 2021

Bibliographical note

Funding Information:
We thank the staff at the cryo-EM facility and instrument core facility in the Hormel Institute, University of Minnesota, which is funded by the Hormel Foundation , for providing help. We also thank the Core Facility and Technical Support of Wuhan Institute of Virology for help in radioactive and fluorescent tests. This work was supported by the starting-up funding from The Hormel Institute , University of Minnesota granted to B.L., the National Natural Science Foundation of China ( 31870133 ) and the Youth Innovation Promotion Association CAS ( Y201750 ) to Y.H.

Publisher Copyright:
© 2021 The Author(s)


  • Biochemistry
  • Biological Sciences
  • Structural Biology


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