7SI3

Consensus structure of ATP7B

Summary for 7SI3

• Entry DOI: 10.2210/pdb7si3/pdb
• EMDB information: 25137
• Descriptor: P-type Cu(+) transporter, MAGNESIUM ION, TETRAFLUOROALUMINATE ION (3 entities in total)
• Functional Keywords: copper transport, wilson disease, metal transport, metal transport-translocase complex, metal transport/translocase
• Biological source: Xenopus tropicalis (Western clawed frog, Silurana tropicalis)
• Total number of polymer chains: 1
• Total formula weight: 159805.95

Authors

Bitter, R.M.,Oh, S.C.,Hite, R.K.,Yuan, P. (deposition date: 2021-10-12, release date: 2022-03-16, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.19 Å)