Cellular distribution of copper to superoxide dismutase involves scaffolding by membranes

Efficient delivery of copper ions to specific intracellular targets requires copper chaperones that acquire metal cargo through unknown mechanisms. Here we demonstrate that the human and yeast copper chaperones (CCS) for superoxide dismutase 1 (SOD1), long thought to exclusively reside in the cytoso...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-12, Vol.110 (51), p.20491-20496
Main Authors: Pope, Christopher R., De Feo, Christopher J., Unger, Vinzenz M.
Format: Article
Language:English
Subjects:
Biological Sciences
Biological Transport, Active - physiology
Cell membranes
Copper
Copper - metabolism
Cytosol - metabolism
Enzyme Activation - physiology
Freight
Genetic Complementation Test
Humans
Intracellular Membranes - metabolism
Lipid Bilayers - metabolism
Lipids
Liposomes
Membranes
Microbiology
Molecular Chaperones - genetics
Molecular Chaperones - metabolism
P branes
Proteins
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
Superoxide Dismutase-1
Superoxides
T tests
Yeast
Yeasts
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Summary:Efficient delivery of copper ions to specific intracellular targets requires copper chaperones that acquire metal cargo through unknown mechanisms. Here we demonstrate that the human and yeast copper chaperones (CCS) for superoxide dismutase 1 (SOD1), long thought to exclusively reside in the cytosol and mitochondrial intermembrane space, can engage negatively charged bilayers through a positively charged lipid-binding interface. The significance of this membrane-binding interface is established through SOD1 activity and genetic complementation studies in Saccharomyces cerevisiae , showing that recruitment of CCS to the membrane is required for activation of SOD1. Moreover, we show that a CCS:SOD1 complex binds to bilayers in vitro and that CCS can interact with human high affinity copper transporter 1. Shifting current paradigms, we propose that CCS-dependent copper acquisition and distribution largely occur at membrane interfaces and that this emerging role of the bilayer may reflect a general mechanistic aspect of cellular transition metal ion acquisition.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1309820110