Crystal structure of a copper-transporting PIB-type ATPase

Nature. 2011 Jun 29;475(7354):59-64. doi: 10.1038/nature10191.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Biological Transport
  • Calcium
  • Cation Transport Proteins / genetics
  • Cell Membrane / metabolism
  • Copper / metabolism*
  • Copper-Transporting ATPases
  • Crystallography, X-Ray
  • Cytoplasm / metabolism
  • Hepatolenticular Degeneration / genetics
  • Humans
  • Legionella pneumophila / chemistry*
  • Menkes Kinky Hair Syndrome / genetics
  • Models, Molecular
  • Mutation, Missense / genetics
  • Protein Structure, Tertiary
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / chemistry
  • Structure-Activity Relationship


  • Bacterial Proteins
  • Cation Transport Proteins
  • CopA protein, Bacteria
  • Copper
  • Adenosine Triphosphatases
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • ATP7A protein, human
  • ATP7B protein, human
  • Copper-Transporting ATPases
  • Calcium

Associated data

  • PDB/3RFU