Structure of a Wbl protein and implications for NO sensing by M. tuberculosis

Bassam K. Kudhair, Andrea M. Hounslow, Matthew D. Rolfe, Jason C. Crack, Debbie M. Hunt, Roger S. Buxton, Laura J. Smith, Nick E. Le Brun, Michael P. Williamson, Jeffrey Green (Lead Author)

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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 α-helices held together by a [4Fe-4S] cluster. The iron–sulfur cluster is required for formation of a complex with the major sigma factor (σA) 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.
Original languageEnglish
Article number2280
JournalNature Communications
Publication statusPublished - 22 Dec 2017

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