8j7t
From Proteopedia
Cryo-EM structure of hZnT7-Fab complex in zinc-unbound state, determined in outward-facing conformation
Structural highlights
DiseaseZNT7_HUMAN The disease may be caused by variants affecting the gene represented in this entry. FunctionZNT7_HUMAN Zinc ion transporter mediating zinc entry from the cytosol into the lumen of organelles along the secretory pathway (PubMed:15525635, PubMed:15994300). By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases (PubMed:15525635, PubMed:15994300).[1] [2] Publication Abstract from PubMedZinc ions (Zn(2+)) are vital to most cells, with the intracellular concentrations of Zn(2+) being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 A-resolution cryo-EM structures of a Golgi-localized human Zn(2+)/H(+) antiporter ZnT7 (hZnT7) in Zn(2+)-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn(2+)-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn(2+) entry in the inward-facing conformation and widens the luminal cavity for Zn(2+) release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn(2+) ions, seemingly facilitating Zn(2+) recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn(2+) uptake into the Golgi to be proposed. Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn(2+) uptake into the Golgi apparatus.,Bui HB, Watanabe S, Nomura N, Liu K, Uemura T, Inoue M, Tsutsumi A, Fujita H, Kinoshita K, Kato Y, Iwata S, Kikkawa M, Inaba K Nat Commun. 2023 Aug 8;14(1):4770. doi: 10.1038/s41467-023-40521-5. PMID:37553324[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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