5oay | pdb_00005oay
M. tuberculosis [4Fe-4S] protein WhiB1 is a four-helix bundle that forms a NO-sensitive complex with sigmaA and regulates the major virulence factor ESX-1
Structural highlights
FunctionWHIB1_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 PubMedMycobacterium 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
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