Structure of a Wbl protein and implications for NO sensing by M. tuberculosis.
Bassam K KudhairAndrea M HounslowMatthew D RolfeJason C CrackDebbie M HuntRoger S BuxtonLaura J SmithNick E Le BrunMichael P WilliamsonJeffrey GreenPublished in: Nature communications (2017)
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.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- dna binding
- gene expression
- nitric oxide
- protein protein
- transcription factor
- amino acid
- escherichia coli
- pseudomonas aeruginosa
- binding protein
- magnetic resonance
- emergency department
- iron deficiency
- hiv infected
- high resolution
- cystic fibrosis
- cancer therapy
- solid state
- pluripotent stem cells
- metal organic framework