Crystal structure of a copper-transporting PIB-type ATPase
Research output: Contribution to journal › Journal article › Research › peer-review
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.
|Number of pages||6|
|Publication status||Published - 7 Jul 2011|
- Adenosine Triphosphatases, Bacterial Proteins, Binding Sites, Biological Transport, Calcium, Cation Transport Proteins, Cell Membrane, Copper, Crystallography, X-Ray, Cytoplasm, Hepatolenticular Degeneration, Humans, Legionella pneumophila, Menkes Kinky Hair Syndrome, Models, Molecular, Mutation, Missense, Protein Structure, Tertiary, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Structure-Activity Relationship