Structural insights into the functional divergence of WhiB-like proteins in Mycobacterium tuberculosis

Tao Wan, Magdaléna Horová, Daisy Guiza Beltran, Shanren Li, Huey Xian Wong, Li Mei Zhang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


WhiB7 represents a distinct subclass of transcription factors in the WhiB-Like (Wbl) family, a unique group of iron-sulfur (4Fe-4S] cluster-containing proteins exclusive to the phylum of Actinobacteria. In Mycobacterium tuberculosis (Mtb), WhiB7 interacts with domain 4 of the primary sigma factor (σA4) in the RNA polymerase holoenzyme and activates genes involved in multiple drug resistance and redox homeostasis. Here, we report crystal structures of the WhiB7:σA4 complex alone and bound to its target promoter DNA at 1.55-Å and 2.6-Å resolution, respectively. These structures show how WhiB7 regulates gene expression by interacting with both σA4 and the AT-rich sequence upstream of the −35 promoter DNA via its C-terminal DNA-binding motif, the AT-hook. By combining comparative structural analysis of the two high-resolution σA4-bound Wbl structures with molecular and biochemical approaches, we identify the structural basis of the functional divergence between the two distinct subclasses of Wbl proteins in Mtb.

Original languageEnglish (US)
Pages (from-to)2887-2900.e5
JournalMolecular Cell
Issue number14
StatePublished - Jul 15 2021


  • AT-hook
  • Wbl family
  • WhiB1
  • WhiB7
  • X-ray crystallography
  • antibiotic resistance
  • iron-sulfur cluster
  • transcription factor
  • σ

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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