8ZSB

Cryo-EM structure of human ZnT1, in the absence of zinc, determined in outward-facing conformation

Summary for 8ZSB

• Entry DOI: 10.2210/pdb8zsb/pdb
• EMDB information: 60410
• Descriptor: Proton-coupled zinc antiporter SLC30A1, ZINC ION (2 entities in total)
• Functional Keywords: copper uptake, cuproptosis, znt family, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 110856.03

Authors

Ma, J.,Zheng, S. (deposition date: 2024-06-05, release date: 2024-08-21, Last modification date: 2025-07-23)

Primary citation

Li, Y.,Ma, J.,Wang, R.,Luo, Y.,Zheng, S.,Wang, X.
Zinc transporter 1 functions in copper uptake and cuproptosis.
Cell Metab., 36:2118-, 2024

PubMed Abstract: Copper (Cu) is a co-factor for several essential metabolic enzymes. Disruption of Cu homeostasis results in genetic diseases such as Wilson's disease. Here, we show that the zinc transporter 1 (ZnT1), known to export zinc (Zn) out of the cell, also mediates Cu entry into cells and is required for Cu-induced cell death, cuproptosis. Structural analysis and functional characterization indicate that Cu and Zn share the same primary binding site, allowing Zn to compete for Cu uptake. Among ZnT members, ZnT1 harbors a unique inter-subunit disulfide bond that stabilizes the outward-open conformations of both protomers to facilitate efficient Cu transport. Specific knockout of the ZnT1 gene in the intestinal epithelium caused the loss of Lgr5+ stem cells due to Cu deficiency. ZnT1, therefore, functions as a dual Zn and Cu transporter and potentially serves as a target for using Zn in the treatment of Wilson's disease caused by Cu overload.

PubMed: 39111308
DOI: 10.1016/j.cmet.2024.07.009

Experimental method

ELECTRON MICROSCOPY (3.26 Å)