Copper-transporting P-type ATPases use a unique ion-release pathway.

Nature structural & molecular biology (2013-12-10)
Magnus Andersson, Daniel Mattle, Oleg Sitsel, Tetyana Klymchuk, Anna Marie Nielsen, Lisbeth Birk Møller, Stephen H White, Poul Nissen, Pontus Gourdon
RESUMO

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.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
Copper, powder, <425 μm, 99.5% trace metals basis
Sigma-Aldrich
Copper, foil, thickness 0.25 mm, 99.98% trace metals basis
Sigma-Aldrich
Copper, powder, 99.999% trace metals basis
Sigma-Aldrich
Copper, wire, diam. 1.0 mm, ≥99.9%
Sigma-Aldrich
Copper, ACS reagent, granular, 10-40 mesh, ≥99.90%
Sigma-Aldrich
Copper, nanopowder, 60-80 nm particle size (SAXS), ≥99.5% trace metals basis
Sigma-Aldrich
Copper, powder, <75 μm, 99%
Sigma-Aldrich
Copper, nanopowder, 40-60 nm particle size (SAXS), ≥99.5% trace metals basis
Sigma-Aldrich
Copper, powder (spheroidal), 10-25 μm, 98%
Sigma-Aldrich
Copper, foil, thickness 0.025 mm, 99.98% trace metals basis
Sigma-Aldrich
Copper, foil, thickness 1.0 mm, 99.999% trace metals basis
Sigma-Aldrich
Copper, foil, thickness 0.5 mm, 99.98% trace metals basis
Sigma-Aldrich
Copper, foil, ≥99.8% (complexometric)
Sigma-Aldrich
Copper, powder (dendritic), <45 μm, 99.7% trace metals basis
Sigma-Aldrich
Copper, bars (random sizes), ≥99.999% trace metals basis
Sigma-Aldrich
Copper, shot, −3-+14 mesh, 99%
Sigma-Aldrich
Copper, rod, diam. 11 mm, 99.9999% trace metals basis
Sigma-Aldrich
Copper, turnings, purum p.a., ≥99.0%
Sigma-Aldrich
Copper, beads, 2-8 mm, ≥99.99% trace metals basis
Sigma-Aldrich
Copper, wire, diam. 0.25 mm, 99.999% trace metals basis
Sigma-Aldrich
Copper, spherical shot, −20-+30 mesh, ≥99.5% trace metals basis
Sigma-Aldrich
Copper, wire, diam. 2.0 mm, 99.999% trace metals basis
Sigma-Aldrich
Copper, electrolytic, Analytical Reagent, reag. Ph. Eur., ≥99.9% (complexometric), wire
Sigma-Aldrich
Copper, beads, 2-8 mm, 99.9995% trace metals basis
Sigma-Aldrich
Copper, wire, diam. 0.64 mm, 99.995% trace metals basis
Sigma-Aldrich
Copper, sputtering target, diam. × thickness 2.00 in. × 0.25 in., 99.95% trace metals basis
Supelco
Copper (impurities), manufactured by MBH Analytical Ltd (39X 17868)
Copper, IRMM®, certified reference material, 0.5 mm wire
Copper, IRMM®, certified reference material, 0.1 mm foil
Copper (S, P), BCR®, certified reference material, chips