| Structural highlights
Function
ZNT1_HUMAN Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (PubMed:31471319). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (By similarity). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (PubMed:32441444).[UniProtKB:Q62720][1] [2]
Publication Abstract from PubMed
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 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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nishito Y, Kambe T. Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels. J Biol Chem. 2019 Oct 25;294(43):15686-15697. PMID:31471319 doi:10.1074/jbc.RA119.010227
- ↑ Stocks CJ, von Pein JB, Curson JEB, Rae J, Phan MD, Foo D, Bokil NJ, Kambe T, Peters KM, Parton RG, Schembri MA, Kapetanovic R, Sweet MJ. Frontline Science: LPS-inducible SLC30A1 drives human macrophage-mediated zinc toxicity against intracellular Escherichia coli. J Leukoc Biol. 2021 Feb;109(2):287-297. PMID:32441444 doi:10.1002/JLB.2HI0420-160R
- ↑ Long Y, Zhu Z, Zhou Z, Yang C, Chao Y, Wang Y, Zhou Q, Wang MW, Qu Q. Structural insights into human zinc transporter ZnT1 mediated Zn(2+) efflux. EMBO Rep. 2024 Oct 10. PMID:39390258 doi:10.1038/s44319-024-00287-3
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