Copper resistance has emerged as an important virulence determinant of microbial pathogens. In Streptococcus pneumoniae, copper resistance is mediated by a sinlge operon including the copper-responsive repressor CopY, CupA and the copper-effluxing P1B-type ATPase CopA. We show that CupA is a unprecedented cell membrane�anchored Cu(I) chaperone and that a Cu(I) binding�competent, membrane-localized CupA is obligatory for copper resistance. We show the crystal structures of the soluble domain of CupA and the metal-binding domain of CopA (CopAMBD) and they reveal isostructural cupredoxin-like folds each harboring a binuclear Cu(I) cluster unprecedented in bacterial copper trafficking. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/239nm/uploads/9848_figure1.jpg' alt='' /> NMR studies reveal unidirectional Cu(I) transfer from the low-affinity site on CupA to the high-affinity site of CopAMBD. However, copper binding by CopAMBDis not essential for copper resistance. Current efforts is made towards assigning the functional role of the individual Cu(I) site and solving the apo CupA structure.Grants:NIH GM042569 to D.P.G., GM094472 to C.E.D. III, AI095814 to M.E.W. GM069696 to M.J.M.

New structural paradigm in copper resistance in Streptococcus pneumoniae

246th National Meeting (2013)

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