4BBJ

Copper-transporting PIB-ATPase in complex with beryllium fluoride representing the E2P state

4BBJ の概要

• エントリーDOI: 10.2210/pdb4bbj/pdb
• 分子名称: COPPER EFFLUX ATPASE, MAGNESIUM ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (6 entities in total)
• 機能のキーワード: hydrolase, cation transport proteins, cell membrane, hepatolenticular degeneration, menkes disease, wilson disease, sarcoplasmic reticulum calcium-transporting atpases, structure-activity relationship, membrane protein
• 由来する生物種: LEGIONELLA PNEUMOPHILA SUBSP. PNEUMOPHILA
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 79806.53

構造登録者

Mattle, D.,Gourdon, P.,Nissen, P. (登録日: 2012-09-25, 公開日: 2013-12-11, 最終更新日: 2024-11-06)

主引用文献

Andersson, M.,Mattle, D.,Sitsel, O.,Klymchuk, T.,Nielsen, A.,Moller, L.B.,White, S.H.,Nissen, P.,Gourdon, P.
Copper-Transporting P-Type Atpases Use a Unique Ion-Release Pathway
Nat.Struct.Mol.Biol., 21:43-, 2014

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.

PubMed: 24317491
DOI: 10.1038/NSMB.2721

実験手法

X-RAY DIFFRACTION (2.75 Å)