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Proceedings of the National Academy of Sciences - PNAS, 2018-04, Vol.115 (15), p.3942-3947
2018

Details

Autor(en) / Beteiligte
Titel
Mechanistic insights into staphylopine-mediated metal acquisition
Ist Teil von
  • Proceedings of the National Academy of Sciences - PNAS, 2018-04, Vol.115 (15), p.3942-3947
Ort / Verlag
United States: National Academy of Sciences
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Electronic Journals Library - Freely accessible e-journals
Beschreibungen/Notizen
  • Metal acquisition is vital to pathogens for successful infection within hosts. Staphylopine (StP), a broad-spectrum metallophore biosynthesized by the major human pathogen, Staphylococcus aureus, plays a central role in transition-metal acquisition and bacterial virulence. The StP-like biosynthesis loci are present in various pathogens, and the proteins responsible for StP/metal transportation have been determined. However, the molecular mechanisms of how StP/metal complexes are recognized and transported remain unknown. We report multiple structures of the extracytoplasmic solute-binding protein CntA from the StP/metal transportation system in apo form and in complex with StP and three different metals. We elucidated a sophisticated metal-bound StP recognition mechanism and determined that StP/metal binding triggers a notable interdomain conformational change in CntA. Furthermore, CRISPR/Cas9-mediated single-base substitution mutations and biochemical analysis highlight the importance of StP/metal recognition for StP/metal acquisition. These discoveries provide critical insights into the study of novel metal-acquisition mechanisms in microbes.

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