4F2E

Crystal structure of the Streptococcus pneumoniae D39 copper chaperone CupA with Cu(I)

Summary for 4F2E

• Entry DOI: 10.2210/pdb4f2e/pdb
• Related: 4F2F
• Descriptor: CupA, COPPER (I) ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: cupredoxin fold, cu(i) chaperone, metal transport
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 1
• Total formula weight: 11050.13

Authors

Fu, Y.,Dann III, C.E.,Giedroc, D.P. (deposition date: 2012-05-07, release date: 2013-01-30, Last modification date: 2024-02-28)

Primary citation

Fu, Y.,Tsui, H.C.,Bruce, K.E.,Sham, L.T.,Higgins, K.A.,Lisher, J.P.,Kazmierczak, K.M.,Maroney, M.J.,Dann, C.E.,Winkler, M.E.,Giedroc, D.P.
A new structural paradigm in copper resistance in Streptococcus pneumoniae.
Nat.Chem.Biol., 9:177-183, 2013

PubMed Abstract: 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.

PubMed: 23354287
DOI: 10.1038/nchembio.1168

Experimental method

X-RAY DIFFRACTION (1.449 Å)