Nature chemical biology, 2013-03, Vol.9 (3), p.177
2013
Details
- Autor(en) / Beteiligte
- Titel
- A new structural paradigm in copper resistance in Streptococcus pneumoniae
- Ist Teil von
- Nature chemical biology, 2013-03, Vol.9 (3), p.177
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Copper resistance has emerged as an important virulence determinant of microbial pathogens. In Streptococcus pneumoniae, copper resistance is mediated by the copper-responsive repressor CopY, CupA and the copper-effluxing P(1B)-type ATPase CopA. We show here that CupA is a previously uncharacterized cell membrane-anchored Cu(I) chaperone and that a Cu(I) binding-competent, membrane-localized CupA is obligatory for copper resistance. The crystal structures of the soluble domain of CupA and the N-terminal metal-binding domain (MBD) of CopA (CopA(MBD)) reveal isostructural cupredoxin-like folds that each harbor a binuclear Cu(I) cluster unprecedented in bacterial copper trafficking. NMR studies reveal unidirectional Cu(I) transfer from the low-affinity site on the soluble domain of CupA to the high-affinity site of CopA(MBD). However, copper binding by CopA(MBD) is not essential for cellular copper resistance, consistent with a primary role of CupA in cytoplasmic Cu(I) sequestration and/or direct delivery to the transmembrane site of CopA for cellular efflux.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1552-4469DOI: 10.1038/nchembio.1168Titel-ID: cdi_pubmed_primary_23354287
- Format
- –
- Schlagworte
- Bacterial Proteins - chemistry, Bacterial Proteins - genetics, Bacterial Proteins - metabolism, Binding Sites, Cell Membrane - chemistry, Cell Membrane - metabolism, Copper - metabolism, Copper - pharmacology, Crystallography, X-Ray, Drug Resistance, Bacterial - drug effects, Drug Resistance, Bacterial - genetics, Magnetic Resonance Spectroscopy, Models, Molecular, Mutation - genetics, Protein Structure, Tertiary, Streptococcus pneumoniae - chemistry, Streptococcus pneumoniae - drug effects, Streptococcus pneumoniae - metabolism, Streptococcus pneumoniae - pathogenicity