Journal
NATURE
Volume 475, Issue 7354, Pages 59-U74Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature10191
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Funding
- Danish Natural Science Research Council
- Swedish Research Council
- China Scholarship Council
- Carlsberg Foundation
- European Research Council
- Novo Nordisk Foundation
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Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu+-ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 angstrom resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca2+-ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases.
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