Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Miyagi, 980-8577, Japan.
Department of Molecular and Chemical Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, 980-8577, Japan.
Nat Commun. 2023 Aug 8;14(1):4770. doi: 10.1038/s41467-023-40521-5.
Zinc ions (Zn) are vital to most cells, with the intracellular concentrations of Zn 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/H antiporter ZnT7 (hZnT7) in Zn-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-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn entry in the inward-facing conformation and widens the luminal cavity for Zn release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn ions, seemingly facilitating Zn recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn uptake into the Golgi to be proposed.
锌离子（Zn）对大多数细胞至关重要，细胞内的 Zn 浓度由位于质膜和细胞器膜上的多种锌转运体严格调控。本文呈现了定位于高尔基体的人 Zn/H 反向转运蛋白 ZnT7（hZnT7）在结合和未结合 Zn 形式下的 2.2-3.1Å 分辨率冷冻电镜结构。冷冻电镜分析表明，hZnT7 通过两个同源物的胞质和跨膜（TM）结构域之间的紧密相互作用形成二聚体，每个同源物的 TM 结构域都含有一个单独的 Zn 结合位点。hZnT7 的 TM 螺旋发生重排，在内向构象中形成带负电荷的胞质腔以利于 Zn 进入，在外向构象中扩大腔室以利于 Zn 释放。hZnT7 特有的长胞质组氨酸富含环结合两个 Zn 离子，似乎促进了 Zn 向 TM 金属转运途径的募集。这些结构允许提出 hZnT7 介导的 Zn 进入高尔基体的机制。
