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TitleStructures of the human Wilson disease copper transporter ATP7B.
Journal, issue, pagesCell Rep, Vol. 42, Issue 5, Page 112417, Year 2023
Publish dateApr 18, 2023
AuthorsGuo-Min Yang / Lingyi Xu / Rou-Min Wang / Xin Tao / Zi-Wei Zheng / Shenghai Chang / Demin Ma / Cheng Zhao / Yi Dong / Shan Wu / Jiangtao Guo / Zhi-Ying Wu /
PubMed AbstractThe P-type ATPase ATP7B exports cytosolic copper and plays an essential role in the regulation of cellular copper homeostasis. Mutants of ATP7B cause Wilson disease (WD), an autosomal recessive ...The P-type ATPase ATP7B exports cytosolic copper and plays an essential role in the regulation of cellular copper homeostasis. Mutants of ATP7B cause Wilson disease (WD), an autosomal recessive disorder of copper metabolism. Here, we present cryoelectron microscopy (cryo-EM) structures of human ATP7B in the E1 state in the apo, the putative copper-bound, and the putative cisplatin-bound forms. In ATP7B, the N-terminal sixth metal-binding domain (MBD6) binds at the cytosolic copper entry site of the transmembrane domain (TMD), facilitating the delivery of copper from the MBD6 to the TMD. The sulfur-containing residues in the TMD of ATP7B mark the copper transport pathway. By comparing structures of the E1 state human ATP7B and E2-P state frog ATP7B, we propose the ATP-driving copper transport model of ATP7B. These structures not only advance our understanding of the mechanisms of ATP7B-mediated copper export but can also guide the development of therapeutics for the treatment of WD.
External linksCell Rep / PubMed:37074913
MethodsEM (single particle)
Resolution3.3 - 4.0 Å
Structure data

33472

7xuk

EMDB-33472, PDB-7xuk:
Structure of ATP7B C983S/C985S/D1027A mutant in presence of ATOX1
Method: EM (single particle) / Resolution: 3.3 Å

33474

7xum

EMDB-33474, PDB-7xum:
Structure of ATP7B C983S/C985S/D1027A mutant with Cu+ in presence of ATOX1
Method: EM (single particle) / Resolution: 3.8 Å

33475

7xun

EMDB-33475, PDB-7xun:
Structure of ATP7B C983S/C985S/D1027A mutant
Method: EM (single particle) / Resolution: 3.4 Å

33476

7xuo

EMDB-33476, PDB-7xuo:
Structure of ATP7B C983S/C985S/D1027A mutant with cisplatin in presence of ATOX1
Method: EM (single particle) / Resolution: 3.6 Å

35628

8ioy

EMDB-35628, PDB-8ioy:
Structure of ATP7B C983S/C985S/D1027A mutant with AMP-PNP
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-CU:
COPPER (II) ION / Copper

ChemComp-PT:
Unknown entry

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
KeywordsTRANSLOCASE / P-type Cu(+) transporter / TRANSLOCATE / METAL TRANSPORT / METAT TRANSPORT / ATOX1 / cisplatin

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