Crystal structure of a copper-transporting PIB-type ATPase

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  • Pontus Gourdon, Danmark
  • Xiang-Yu Liu, Peking University , Kina
  • Tina Skjørringe, Kennedy Centret, Danmark
  • J Preben Morth, Danmark
  • Lisbeth Birk Møller, Kennedy Centret, Danmark
  • Bjørn Panyella Pedersen
  • Poul Nissen
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 Å 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 Ca(2+)-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.
OriginalsprogEngelsk
TidsskriftNature
Vol/bind475
Nummer7354
Sider (fra-til)59-64
Antal sider6
ISSN0028-0836
DOI
StatusUdgivet - 29 jun. 2011

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