7KUG

Fe-S cluster-bound transcription activator WhiB7 in complex with the SigmaAr4-RNAP Beta flap tip chimera

Summary for 7KUG

• Entry DOI: 10.2210/pdb7kug/pdb
• Descriptor: Probable transcriptional regulator WhiB7, RNA polymerase sigma factor, DNA-directed RNA polymerase subunit beta chimera, IRON/SULFUR CLUSTER, ... (4 entities in total)
• Functional Keywords: redox-sensitive, iron-sulfur cluster, transcription, activator
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); More
• Total number of polymer chains: 4
• Total formula weight: 43862.88

Authors

Wan, T.,Horova, M.,Beltran, D.G.,Li, S.R.,Zhang, L.M. (deposition date: 2020-11-24, release date: 2021-06-30, Last modification date: 2024-10-16)

Primary citation

Wan, T.,Horova, M.,Beltran, D.G.,Li, S.,Wong, H.X.,Zhang, L.M.
Structural insights into the functional divergence of WhiB-like proteins in Mycobacterium tuberculosis.
Mol.Cell, 81:2887-, 2021

PubMed Abstract: 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 (σ) in the RNA polymerase holoenzyme and activates genes involved in multiple drug resistance and redox homeostasis. Here, we report crystal structures of the WhiB7:σ 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 σ 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 σ-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.

PubMed: 34171298
DOI: 10.1016/j.molcel.2021.06.002

Experimental method

X-RAY DIFFRACTION (1.55 Å)