Crystal structure of a copper-transporting PIB-type ATPase

Pontus Gourdon, Xiang-Yu Liu, Tina Skjørringe, J Preben Morth, Lisbeth Birk Møller, Bjørn Panyella Pedersen, Poul Nissen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

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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