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

Kudhair, Bassam K., Hounslow, Andrea M., Rolfe, Matthew D., Crack, Jason C., Hunt, Debbie M., Buxton, Roger S., Smith, Laura J., Le Brun, Nick E. ORCID: https://orcid.org/0000-0001-9780-4061, Williamson, Michael P. and Green, Jeffrey (2017) Structure of a Wbl protein and implications for NO sensing by M. tuberculosis. Nature Communications, 8. ISSN 2041-1723

Preview

PDF (s41467-017-02418-y) - Published Version Available under License Creative Commons Attribution. Download (3MB) | Preview

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 (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.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Chemistry
UEA Research Groups:	Faculty of Science > Research Groups > Centre for Ocean and Atmospheric Sciences Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry Faculty of Science > Research Groups > Chemistry of Life Processes
Depositing User:	Pure Connector
Date Deposited:	15 Dec 2017 13:36
Last Modified:	22 Oct 2022 03:25
URI:	https://ueaeprints.uea.ac.uk/id/eprint/65743
DOI:	10.1038/s41467-017-02418-y

Actions (login required)

View Item