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TitleStructure of the Wilson disease copper transporter ATP7B.
Journal, issue, pagesSci Adv, Vol. 8, Issue 9, Page eabl5508, Year 2022
Publish dateMar 4, 2022
AuthorsRyan M Bitter / SeCheol Oh / Zengqin Deng / Suhaila Rahman / Richard K Hite / Peng Yuan /
PubMed AbstractATP7A 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 ...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.
External linksSci Adv / PubMed:35245129 / PubMed Central
MethodsEM (single particle)
Resolution3.19 - 3.49 Å
Structure data

25137

7si3

EMDB-25137, PDB-7si3:
Consensus structure of ATP7B
Method: EM (single particle) / Resolution: 3.19 Å

25138

7si6

EMDB-25138, PDB-7si6:
Structure of ATP7B in state 1
Method: EM (single particle) / Resolution: 3.32 Å

25139

7si7

EMDB-25139, PDB-7si7:
Structure of ATP7B in state 2
Method: EM (single particle) / Resolution: 3.49 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ALF:
TETRAFLUOROALUMINATE ION

Source
  • xenopus tropicalis (tropical clawed frog)
KeywordsMETAL TRANSPORT/Translocase / Copper transport / Wilson disease / METAL TRANSPORT / METAL TRANSPORT-Translocase complex / Translocase

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