EMD-36055
Cryo-EM structure of hZnT7-Fab complex in zinc state 1, determined in heterogeneous conformations- one subunit in an inward-facing zinc-bound and the other in an outward-facing zinc-unbound conformation
EMD-36055
Single-particle2.68 Å
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Map released: 20/09/2023
Last modified: 23/10/2024
Sample Organism:
Homo sapiens,
Mus musculus
Sample: Human ZnT7-Fab complex
Fitted models: 8j80 (Avg. Q-score: 0.504)
Deposition Authors: Han BB, Inaba K
,
Watanabe S
Sample: Human ZnT7-Fab complex
Fitted models: 8j80 (Avg. Q-score: 0.504)
Deposition Authors: Han BB, Inaba K
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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
(2023) Nat Commun , 14 , 4770 - 4770
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(2023) Nat Commun , 14 , 4770 - 4770
Abstract:
Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in Zn2+-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 Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing conformation and widens the luminal cavity for Zn2+ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn2+ ions, seemingly facilitating Zn2+ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi to be proposed.
Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in Zn2+-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 Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing conformation and widens the luminal cavity for Zn2+ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn2+ ions, seemingly facilitating Zn2+ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi to be proposed.