RRC ID |
82558
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Author |
Ishida H, Yo R, Zhang Z, Shimizu T, Ohto U.
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Title |
Cryo-EM structures of the zinc transporters ZnT3 and ZnT4 provide insights into their transport mechanisms.
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Journal |
FEBS Lett
|
Abstract |
Zinc transporters (ZnTs) act as H+/Zn2+ antiporters, crucial for zinc homeostasis. Brain-specific ZnT3 expressed in synaptic vesicles transports Zn2+ from the cytosol into vesicles and is essential for neurotransmission, with ZnT3 dysfunction associated with neurological disorders. Ubiquitously expressed ZnT4 localized to lysosomes facilitates the Zn2+ efflux from the cytosol to lysosomes, mitigating the cell injury risk. Despite their importance, the structures and Zn2+ transport mechanisms remain unclear. We characterized the three-dimensional structures of human ZnT3 (inward-facing) and ZnT4 (outward-facing) using cryo-electron microscopy. By combining these structures, we assessed the conformational changes that could occur within the transmembrane domain during Zn2+ transport. Our results provide a structural basis for a more comprehensive understanding of the H+/Zn2+ exchange mechanisms exhibited by ZnTs.
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Published |
2024-10-30
|
DOI |
10.1002/1873-3468.15047
|
PMID |
39474773
|
Resource |
DNA material |
Genome Network Project (GNP) Human cDNA
IRAK034H19 (HGY013787)
IRAK034M01 (HGY013889) |