The heme-sensitive regulator SbnI has a bifunctional role in staphyloferrin B production by Staphylococcus aureus
Year: 2019
Type: article
Abstract: Staphylococcus aureus infection relies on iron acquisition from its host. S. aureus takes up iron through heme uptake by the iron-responsive surface determinant (Isd) system and by the production of iron-scavenging siderophores. Staphyloferrin B (SB) is a siderophore produced by the 9-gene sbn gene cluster for SB biosynthesis and efflux. Recently, the ninth gene product, SbnI, was determined to be a free l-serine kinase that produces O- phospho-l-serine (OPS), a substrate for SB biosynthesis. Previous studies have also characterized SbnI as a DNA-binding regulatory protein that senses heme to control sbn gene expression for SB synthesis. Here, we present crystal structures at 1.9–2.1 Å resolution of a SbnI homolog from Staphylococcus pseudintermedius (SpSbnI) in both apo form and in complex with ADP, a product of the kinase reaction; the latter confirmed the active-site location. The structures revealed that SpSbnI forms a dimer through C-terminal domain swapping and a dimer of dimers through intermolecular disulfide formation. Heme binding had only a modest effect on SbnI enzymatic activity, suggesting that its two functions are independent and structurally distinct. We identified a heme-binding site and observed catalytic heme transfer between a heme-degrading protein of the Isd system, IsdI, and SbnI. These findings support the notion that SbnI has a bifunctional role contributing precursor OPS to SB synthesis and directly sensing heme to control expression of the sbn locus. We propose that heme transfer from IsdI to SbnI enables S. aureus to control iron source preference according to the sources available in the environment.
Source: Journal of Biological Chemistry
Institutions: University of British Columbia, Western University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: U.S. Department of Energy, Canadian Light Source, University of Saskatchewan, Government of Canada, National Institutes of Health, Office of Science, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Western Economic Diversification Canada, National Research Council Canada, National Institute of General Medical Sciences, Basic Energy Sciences, Biological and Environmental Research, SLAC National Accelerator Laboratory
Awards: G1229526393, G1286251239, G1804828992, G1831385526, G1842539602, G2371548206, G262532246, G303061748, G315621713, G3488436650, G3629260272, G3735011448, G4235786860, G4280418065, G4581610328, G463712595, G4908923434, G495301720, G498139845, G5108749866, G5570207115, G628751139, G6550344761, G7083997402, G7283024673, G7313278570, G8382000481, A Synchrotron Radiation Structural Biology Resource, G8925327636, G9000081332, G911061179, G937147498, G969889393
OpenAlex ID: W2951276752