Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus

Bui, H. B.; Watanabe, S.; Nomura, N.; Liu, K.; Uemura, T.; Inoue, M.; Tsutsumi, A.; Fujita, H.; Kinoshita, K.; Iwata, S.; Kikkawa, M.; Inaba, K.

doi:10.1101/2022.03.23.485435

bioRxiv · 10.1101/2022.03.23.485435

Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus

Bui, H. B.·Watanabe, S.·Nomura, N.·Liu, K.·Uemura, T.·Inoue, M.·Tsutsumi, A.·Fujita, H.·Kinoshita, K.·Iwata, S.·Kikkawa, M.·Inaba, K.

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Abstract

Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.8-2.9 [A]-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in its outward- and inward-facing forms. Cryo-EM analyses showed that hZnT7 exists as a homodimer via tight interactions in both the cytosolic and transmembrane (TM) regions of two protomers, each of which contains a single Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing form and a widened luminal cavity for Zn2+ release in the outward-facing form. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 can bind at least two Zn2+ ions, likely facilitating Zn2+ recruitment from the cytosol. Unique mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi are proposed.

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Bui, H. B., Watanabe, S., Nomura, N., Liu, K., Uemura, T., Inoue, M., Tsutsumi, A., Fujita, H., Kinoshita, K., Iwata, S., Kikkawa, M., Inaba, K.. 2022-03-23. Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus. https://doi.org/10.1101/2022.03.23.485435

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