7SI6

Structure of ATP7B in state 1

7SI6 の概要

• エントリーDOI: 10.2210/pdb7si6/pdb
• EMDBエントリー: 25138
• 分子名称: P-type Cu(+) transporter, MAGNESIUM ION, TETRAFLUOROALUMINATE ION (3 entities in total)
• 機能のキーワード: copper transport, wilson disease, metal transport, translocase
• 由来する生物種: Xenopus tropicalis (Western clawed frog, Silurana tropicalis)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 159805.95

構造登録者

Bitter, R.M.,Oh, S.C.,Hite, R.K.,Yuan, P. (登録日: 2021-10-12, 公開日: 2022-03-16, 最終更新日: 2024-11-13)

主引用文献

Bitter, R.M.,Oh, S.,Deng, Z.,Rahman, S.,Hite, R.K.,Yuan, P.
Structure of the Wilson disease copper transporter ATP7B.
Sci Adv, 8:eabl5508-eabl5508, 2022

PubMed Abstract: ATP7A and ATP7B, two homologous copper-transporting P1B-type ATPases, play crucial roles in cellular copper homeostasis, and mutations cause Menkes and Wilson diseases, respectively. ATP7A/B contains a P-type ATPase core consisting of a membrane transport domain and three cytoplasmic domains, the A, P, and N domains, and a unique amino terminus comprising six consecutive metal-binding domains. Here, we present a cryo-electron microscopy structure of frog ATP7B in a copper-free state. Interacting with both the A and P domains, the metal-binding domains are poised to exert copper-dependent regulation of ATP hydrolysis coupled to transmembrane copper transport. A ring of negatively charged residues lines the cytoplasmic copper entrance that is presumably gated by a conserved basic residue sitting at the center. Within the membrane, a network of copper-coordinating ligands delineates a stepwise copper transport pathway. This work provides the first glimpse into the structure and function of ATP7 proteins and facilitates understanding of disease mechanisms and development of rational therapies.

PubMed: 35245129
DOI: 10.1126/sciadv.abl5508

実験手法

ELECTRON MICROSCOPY (3.32 Å)