Crystal structure of a copper-transporting PIB-type ATPase

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Pontus Gourdon
  • Xiang-Yu Liu
  • Tina Skjørringe
  • J Preben Morth
  • Lisbeth Birk Møller
  • Bjørn Panyella Pedersen
  • Poul Nissen
Externa organisationer
  • Aarhus University
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)59-64
TidskriftNature
Volym475
Utgivningsnummer7354
StatusPublished - 2011 jun 29
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa