Structural insights into human zinc transporter ZnT1 mediated Zn²⁺ efflux.

ABSTRACT: 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 coordi

SUBMITTER: Long Y 

PROVIDER: S-EPMC11549101 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature