RRC ID 82558
Author Ishida H, Yo R, Zhang Z, Shimizu T, Ohto U.
Title Cryo-EM structures of the zinc transporters ZnT3 and ZnT4 provide insights into their transport mechanisms.
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.
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)