8xn1
Cryo-EM structure of human ZnT3, in the presence of zinc, determined in an inward-facing conformationCryo-EM structure of human ZnT3, in the presence of zinc, determined in an inward-facing conformation
Structural highlights
FunctionZNT3_HUMAN Probable proton-coupled zinc ion antiporter mediating the import of zinc from cytoplasm into synaptic vesicles and participating to cellular zinc ion homeostasis in the brain.[1] [2] [3] Publication Abstract from PubMedZinc 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 Zn(2+) translocation is coupled with H(+) or Ca(2+) 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 Zn(2+) ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn(2+) 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. Structural insights into human zinc transporter ZnT1 mediated Zn(2+) efflux.,Long Y, Zhu Z, Zhou Z, Yang C, Chao Y, Wang Y, Zhou Q, Wang MW, Qu Q EMBO Rep. 2024 Oct 10. doi: 10.1038/s44319-024-00287-3. PMID:39390258[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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