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Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP0092
Published on: October 2, 2017
A new structural paradigm in copper resistance in Streptococcus pneumoniae
Yue Fu1, Ho-Ching Tiffany Tsui, Kevin E Bruce
1Department of Chemistry, Indiana University, Bloomington, Indiana, USA.
Nature Chemical Biology
|January 29, 2013
Summary
CupA, a novel copper chaperone in Streptococcus pneumoniae, is essential for microbial copper resistance. This protein facilitates copper efflux by delivering copper to the CopA transporter.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Copper resistance is a critical virulence factor in microbial pathogens.
- In Streptococcus pneumoniae, copper resistance involves the CopY repressor, CupA protein, and the CopA copper-effluxing ATPase.
Purpose of the Study:
- To characterize the role of CupA in copper resistance in Streptococcus pneumoniae.
- To elucidate the structural and functional mechanisms of CupA-mediated copper trafficking.
Main Methods:
- Determined crystal structures of the soluble domain of CupA and the N-terminal metal-binding domain of CopA (CopA(MBD)).
- Utilized Nuclear Magnetic Resonance (NMR) spectroscopy to study copper transfer dynamics.
- Investigated the necessity of Cu(I) binding-competent, membrane-localized CupA for cellular copper resistance.
Main Results:
- CupA functions as a cell membrane-anchored copper chaperone essential for copper resistance.
- Both CupA and CopA(MBD) share isostructural cupredoxin-like folds with unprecedented binuclear Cu(I) clusters.
- NMR studies demonstrated unidirectional Cu(I) transfer from CupA to CopA(MBD), suggesting CupA's role in cytoplasmic copper sequestration or delivery to CopA.
Conclusions:
- CupA is a novel, indispensable copper chaperone for Streptococcus pneumoniae copper resistance.
- The structural and functional data reveal a unique bacterial copper trafficking mechanism involving CupA and CopA.
- CupA likely sequesters cytoplasmic copper or directly delivers it to the CopA efflux pump.
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