Structures, Mechanisms, and Physiological Functions of Zinc Transporters in Different Biological Kingdoms

Zinc transporters take up/release zinc ions (Zn²⁺) across biological membranes and maintain intracellular and intra-organellar Zn²⁺ homeostasis. Since this process requires a series of conformational changes in the transporters, detailed information about the structures of different reaction intermediates is required for a comprehensive understanding of their Zn²⁺ transport mechanisms. Recently, various Zn²⁺ transport systems have been identified in bacteria, yeasts, plants, and humans. Based on structural analyses of human ZnT7, human ZnT8, and bacterial YiiP, we propose updated models explaining their mechanisms of action to ensure efficient Zn²⁺ transport. We place particular focus on the mechanistic roles of the histidine-rich loop shared by several zinc transporters, which facilitates Zn²⁺ recruitment to the transmembrane Zn²⁺-binding site. This review provides an extensive overview of the structures, mechanisms, and physiological functions of zinc transporters in different biological kingdoms.