Structural highlights
Function
WHB7A_MYCTU The apo- but not holo-form probably binds DNA (By similarity). Acts as a transcriptional regulator. Probably redox-responsive. Upon overproduction at least 10 other genes are up-regulated, among them are Rv1258c, Rv1988, Rv2301, Rv2416c, Rv2725c and whiB7 itself. Probably redox-responsive. The apo-form has been shown to act as a protein disulfide reductase.[1] [2]
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.
References
- ↑ Morris RP, Nguyen L, Gatfield J, Visconti K, Nguyen K, Schnappinger D, Ehrt S, Liu Y, Heifets L, Pieters J, Schoolnik G, Thompson CJ. Ancestral antibiotic resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12200-5. PMID:16103351 doi:10.1073/pnas.0505446102
- ↑ Alam MS, Garg SK, Agrawal P. Studies on structural and functional divergence among seven WhiB proteins of Mycobacterium tuberculosis H37Rv. FEBS J. 2009 Jan;276(1):76-93. doi: 10.1111/j.1742-4658.2008.06755.x. PMID:19016840 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06755.x
- ↑ Wan T, Horová M, Beltran DG, Li S, Wong HX, Zhang LM. Structural insights into the functional divergence of WhiB-like proteins in Mycobacterium tuberculosis. Mol Cell. 2021 Jul 15;81(14):2887-2900.e5. PMID:34171298 doi:10.1016/j.molcel.2021.06.002
