Abstract
The WhiB4 protein, a member of WhiB-like proteins, plays an important role in the survival and pathology of Mycobacterium tuberculosis (Mtb). As a transcription factor, WhiB4 regulates the expression of genes involved in maintaining redox homeostasis, central metabolism, and respiration. Furthermore, WhiB4 leads to the condensation of mycobacterial nucleoids and is capable of binding to DNA. WhiB4 contains four cysteine residues and exists in multiple forms under different redox environments, including a dimeric holo form with iron-sulfur cluster, multimeric disulfide-linked oxidized apo forms and monomeric reduced apo form. Here, we report the 1H, 13C, 15N chemical shifts of WhiB4 protein in its reduced apo state, providing a basis for the determination of its solution structure.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alam MS, Garg SK, Agrawal P (2007) Molecular function of WhiB4/Rv3681c of Mycobacterium tuberculosis H37Rv: a 4Fe-4S cluster co-ordinating protein disulphide reductase. Mol Microbiol 63:1414–1431
Bush MJ (2018) The actinobacterial WhiB-like (Wbl) family of transcription factors. Mol Microbiol 110:663–676
Chawla M, Parikh P, Saxena A, Munshi M, Mehta M, Mai D, Srivastava AK, Narasimhulu KV, Redding KE, Vashi N, Kumar D, Steyn AJC, Singh A (2012) Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo. Mol Microbiol 85:1148–1165
Chawla M, Mishra S, Anand K, Parikh P, Mehta M, Vij M, Verma T, Singh P, Jakkala K, Verma HN, AjitKumar P, Ganguli M, Seshasayee ASN, Singh A (2018) Redox-dependent condensation of the mycobacterial nucleoid by WhiB4. Redox Biol 19:116–133
Davis NK, Chater KF (1992) The streptomyces-coelicocor-WhiB gene encodes a small transcription factor-like protein dispensable for growth but essential for sporulation. Mol Gen Genet 232:351–358
Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A (1995) Nmrpipe: a multidimensional spectral processing system based on unix pipes. J Biomol NMR 6:277–293
Flardh K, Findlay KC, Chater KF (1999) Association of early sporulation genes with suggested developmental decision points in Streptomyces coelicolor A3(2). Microbiology 145:2229–2243
Geiman DE, Raghunand TR, Agarwal N, Bishai WR (2006) Differential gene expression in response to exposure to antimycobacterial agents and other stress conditions among seven Mycobacterium tuberculosis whiB-like genes. Antimicrob Agents Chemother 50:2836–2841
Johnson BA, Blevins RA (1994) Nmr view: a computer program for the visualization and analysis of nmr data. J Biomol NMR 4:603–614
Markley JL, Bax A, Arata Y, Hilbers CW, Kaptein R, Sykes BD, Wright PE, Wuthrich K (1998) Recommendations for the presentation of nmr structures of proteins and nucleic acids. Iupac-iubmb-iupab inter-union task group on the standardization of data bases of protein and nucleic acid structures determined by nmr spectroscopy. J Biomol NMR 12:1–23
Marsh JA, Singh VK, Jia Z, Forman-Kay JD (2006) Sensitivity of secondary structure propensities to sequence differences between alpha- and gamma-synuclein: implications for fibrillation. Protein Sci 15:2795–2804
Singh A, Guidry L, Narasimhulu KV, Mai D, Trombley J, Redding KE, Giles GI, Lancaster JR Jr, Steyn AJ (2007) Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe–4S] cluster and is essential for nutrient starvation survival. Proc Natl Acad Sci USA 104:11562–11567
Soliveri JA, Gomez J, Bishai WR, Chater KF (2000) Multiple paralogous genes related to the Streptomyces coelicolor developmental regulatory gene whiB are present in Streptomyces and other actinomycetes. Microbiology 146:333–343
Steyn AJC, Collins DM, Hondalus MK, Jacobs WR, Kawakami RP, Bloom BR (2002) Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc Natl Acad Sci USA 99:3147–3152
Wu J, Ru HW, Xiang ZH, Jiang J, Wang YC, Zhang L, Liu J (2017) WhiB4 regulates the PE/PPE gene family and is essential for virulence of Mycobacterium marinum. Sci Rep 7:3007
Acknowledgements
All NMR experiments were performed at the Beijing NMR Center and the NMR facility of National Center for Protein Sciences, at Peking University. This work was supported by Grant 2016YFA0501202 from the Ministry of Science and Technology, Grant 31570734 from the National Natural Science Foundation of China, and Grant 2018YFD0500900 from National Key R&D Program of China. We thank Dr. Hongwei Li and Dr. Xiaogang Niu for their assistance in the NMR experiments.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhai, Q., Lin, C., Duan, B. et al. 1H, 13C, and 15N resonance assignments of reduced apo-WhiB4 from Mycobacterium tuberculosis. Biomol NMR Assign 15, 99–101 (2021). https://doi.org/10.1007/s12104-020-09989-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12104-020-09989-w