Zinc transporter 1 (ZnT1), the principal carrier of cytosolic zinc to the extracellular milieu, is important for cellular zinc homeostasis and resistance to zinc toxicity. Despite recent advancements in the structural characterization of various zinc transporters, the mechanism by which ZnTs-mediated Zn2+ translocation is coupled with H+ or Ca2+ remains unclear. To visualize the transport dynamics, we determined the cryo-electron microscopy (cryo-EM) structures of human ZnT1 at different functional states. ZnT1 dimerizes via extensive interactions between the cytosolic (CTD), the transmembrane (TMD), and the unique cysteine-rich extracellular (ECD) domains. At pH 7.5, both protomers adopt an outward-facing (OF) conformation, with Zn2+ ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn2+ exhibits various conformations [OF/OF, OF/IF (inward-facing), and IF/IF]. These conformational snapshots, together with biochemical investigation and molecular dynamic simulations, shed light on the mechanism underlying the proton-dependence of ZnT1 transport.
Zinc is an essential mineral for human health, and its deficiency can lead to various health issues. Oysters ( Crassostrea gigas ) are known to be a rich source of protein-bound zinc. Oyster peptides were complexed with zinc sulfate (ZnSO 4 ) to be oyster peptide-zinc chelates (OPZs) that offer potential as a valuable zinc supplement. The complexation of zinc with oyster peptides induces conformational changes in the peptides, altering their overall spatial arrangement. This could potentially impact their functions and properties. OPZs have demonstrated enhanced physical and gastrointestinal stability, as they are resistant to digestion by pepsin and trypsin. The research has shown that OPZs can modulate the expression of key proteins involved in zinc binding (MT1), peptide transport (PePT1), and zinc transport (ZIP4 and ZnT1) in enterocytes. By regulating the proteins expression, OPZs have the potential to affect zinc absorption and homeostasis. Furthermore, OPZs have been found to enhance zinc absorption through dual pathways compared to the single pathway of inorganic zinc. Additionally, they have the potential to improve zinc bioaccessibility and bioavailability, meaning they can make zinc more easily absorbed by the body and readily available for use.
危险品化学品经营许可证（带存储）