Download MendeleyCopper-Transporting P-Type Atpases Use a Unique Ion-Release Pathway
Andersson, M., Mattle, D., Sitsel, O., Klymchuk, T., Nielsen, A., Moller, L.B., White, S.H., Nissen, P., Gourdon, P.(2014) Nat Struct Mol Biol 21: 43
- PubMed: 24317491
- DOI: https://doi.org/10.1038/nsmb.2721
- Primary Citation of Related Structures:
4BBJ - PubMed Abstract:
Heavy metals in cells are typically regulated by PIB-type ATPases. The first structure of the class, a Cu(+)-ATPase from Legionella pneumophila (LpCopA), outlined a copper transport pathway across the membrane, which was inferred to be occluded. Here we show by molecular dynamics simulations that extracellular water solvated the transmembrane (TM) domain, results indicative of a Cu(+)-release pathway. Furthermore, a new LpCopA crystal structure determined at 2.8-Å resolution, trapped in the preceding E2P state, delineated the same passage, and site-directed-mutagenesis activity assays support a functional role for the conduit. The structural similarities between the TM domains of the two conformations suggest that Cu(+)-ATPases couple dephosphorylation and ion extrusion differently than do the well-characterized PII-type ATPases. The ion pathway explains why certain Menkes' and Wilson's disease mutations impair protein function and points to a site for inhibitors targeting pathogens.
Organizational Affiliation:
1] Department of Physiology and Biophysics, University of California at Irvine, Irvine, California, USA. [2] [3].
