Structural basis of Streptomyces transcription activation by zinc uptake regulator. Issue 14 (25th July 2022)

• Record Type: Journal Article
• Authors: Yang, Xu; Wang, Yiqun; Liu, Guiyang; Deng, Zixin; Lin, Shuangjun; Zheng, Jianting
• Is Part Of: Nucleic acids research. Volume 50:Issue 14(2022)
• Page Start: 8363
• Page End: 8376
• Publication Date: 2022-07-25
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac627
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Streptomyces coelicolor ( Sc ) is a model organism of actinobacteria to study morphological differentiation and production of bioactive metabolites. Sc zinc uptake regulator (Zur) affects both processes by controlling zinc homeostasis. It activates transcription by binding to palindromic Zur-box sequences upstream of −35 elements. Here we deciphered the molecular mechanism by which Sc Zur interacts with promoter DNA and Sc RNA polymerase (RNAP) by cryo-EM structures and biochemical assays. The Sc Zur-DNA structures reveal a sequential and cooperative binding of three Sc Zur dimers surrounding a Zur-box spaced 8 nt upstream from a −35 element. The Sc RNAPσ HrdB -Zur-DNA structures define protein-protein and protein-DNA interactions involved in the principal housekeeping σ HrdB -dependent transcription initiation from a noncanonical promoter with a −10 element lacking the critical adenine residue at position −11 and a TTGCCC −35 element deviating from the canonical TTGACA motif. Sc Zur interacts with the C-terminal domain of Sc RNAP α subunit (αCTD) in a complex structure trapped in an active conformation. Key Sc Zur-αCTD interfacial residues accounting for Sc Zur-dependent transcription activation were confirmed by mutational studies. Together, our structural and biochemical results provide a comprehensive model for transcription activation of Zur family regulators.