Structure of a Wbl protein and implications for NO sensing by M. tuberculosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29273788.
- Also identified by DOI 10.1038/s41467-017-02418-y and PMC identifier 5741622.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 (σ<sup>A</sup>) 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.
Medical subject headings
- Bacterial Proteins
- DNA
- Iron-Sulfur Proteins
- Mycobacterium tuberculosis
- Nitric Oxide
- Transcription Factors