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Publication Abstract from PubMed

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 (sigma(A)(4)) in the RNA polymerase holoenzyme and activates genes involved in multiple drug resistance and redox homeostasis. Here, we report crystal structures of the WhiB7:sigma(A)(4) complex alone and bound to its target promoter DNA at 1.55-A and 2.6-A resolution, respectively. These structures show how WhiB7 regulates gene expression by interacting with both sigma(A)(4) 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 sigma(A)(4)-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.

Structural insights into the functional divergence of WhiB-like proteins in Mycobacterium tuberculosis.,Wan T, Horova M, Beltran DG, Li S, Wong HX, Zhang LM Mol Cell. 2021 Jul 15;81(14):2887-2900.e5. doi: 10.1016/j.molcel.2021.06.002. , Epub 2021 Jun 24. PMID:34171298^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.