| Structural highlights
Function
WHIB1_MYCTU Acts as a transcriptional repressor, inhibiting expression in vitro. Probably redox-responsive. The apo- but not holo-form binds to its own promoter as well as that of groEL2. Oxidized apo-form and nitrosylated holo-form also bind DNA. The apo-form has been shown to act as a protein disulfide reductase (PubMed:17157031) (PubMed:19016840), but also not to act as a protein disulfide reductase (PubMed:20929442).[1] [2] [3] [4]
Publication Abstract from PubMed
Mycobacterium tuberculosis causes pulmonary tuberculosis (TB) and claims ~1.8 million human lives per annum. Host nitric oxide (NO) is important in controlling TB infection. M. tuberculosis WhiB1 is a NO-responsive Wbl protein (actinobacterial iron-sulfur proteins first identified in the 1970s). Until now, the structure of a Wbl protein has not been available. Here a NMR structural model of WhiB1 reveals that Wbl proteins are four-helix bundles with a core of three alpha-helices held together by a [4Fe-4S] cluster. The iron-sulfur cluster is required for formation of a complex with the major sigma factor (sigma(A)) and reaction with NO disassembles this complex. The WhiB1 structure suggests that loss of the iron-sulfur cluster (by nitrosylation) permits positively charged residues in the C-terminal helix to engage in DNA binding, triggering a major reprogramming of gene expression that includes components of the virulence-critical ESX-1 secretion system.
Structure of a Wbl protein and implications for NO sensing by M. tuberculosis.,Kudhair BK, Hounslow AM, Rolfe MD, Crack JC, Hunt DM, Buxton RS, Smith LJ, Le Brun NE, Williamson MP, Green J Nat Commun. 2017 Dec 22;8(1):2280. doi: 10.1038/s41467-017-02418-y. PMID:29273788[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garg SK, Suhail Alam M, Soni V, Radha Kishan KV, Agrawal P. Characterization of Mycobacterium tuberculosis WhiB1/Rv3219 as a protein disulfide reductase. Protein Expr Purif. 2007 Apr;52(2):422-32. doi: 10.1016/j.pep.2006.10.015. Epub, 2006 Nov 10. PMID:17157031 doi:http://dx.doi.org/10.1016/j.pep.2006.10.015
- ↑ 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
- ↑ Smith LJ, Stapleton MR, Fullstone GJ, Crack JC, Thomson AJ, Le Brun NE, Hunt DM, Harvey E, Adinolfi S, Buxton RS, Green J. Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster. Biochem J. 2010 Dec 15;432(3):417-27. PMID:20929442
- ↑ Stapleton MR, Smith LJ, Hunt DM, Buxton RS, Green J. Mycobacterium tuberculosis WhiB1 represses transcription of the essential chaperonin GroEL2. Tuberculosis (Edinb). 2012 Jul;92(4):328-32. doi: 10.1016/j.tube.2012.03.001., Epub 2012 Mar 29. PMID:22464736 doi:http://dx.doi.org/10.1016/j.tube.2012.03.001
- ↑ Kudhair BK, Hounslow AM, Rolfe MD, Crack JC, Hunt DM, Buxton RS, Smith LJ, Le Brun NE, Williamson MP, Green J. Structure of a Wbl protein and implications for NO sensing by M. tuberculosis. Nat Commun. 2017 Dec 22;8(1):2280. doi: 10.1038/s41467-017-02418-y. PMID:29273788 doi:http://dx.doi.org/10.1038/s41467-017-02418-y
|
