Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn 2+ uptake into the Golgi apparatus.

Zinc ions (Zn 2+ ) are vital to most cells, with the intracellular concentrations of Zn 2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn 2+ /H + antiporter ZnT7 (hZnT7) in Zn 2+ -bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn 2+ -binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn 2+ entry in the inward-facing conformation and widens the luminal cavity for Zn 2+ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn 2+ ions, seemingly facilitating Zn 2+ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn 2+ uptake into the Golgi to be proposed.