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

doi:10.1016/j.isci.2021.102449

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

iScience. 2021 Apr 16;24(5):102449. doi: 10.1016/j.isci.2021.102449. eCollection 2021 May 21.

Authors

Wei Shi¹, Baoyue Zhang^{2

3}, Yanan Jiang^{1

4}, Chang Liu⁵, Wei Zhou^{2

3}, Ming Chen^{2

3}, Yang Yang^{6

7

8}, Yangbo Hu², Bin Liu¹

Affiliations

¹ Section of Transcription & Gene Regulation, The Hormel Institute, University of Minnesota, Austin, MN, USA.
² State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
³ University of Chinese Academy of Sciences, Beijing, China.
⁴ Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
⁵ Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
⁶ Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.
⁷ Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
⁸ Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.

Abstract

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.

Keywords: Biochemistry; Biological Sciences; Structural Biology.

Grants and funding

UL1 TR001863/TR/NCATS NIH HHS/United States