EMD-38465

Single-particle
3.48 Å
EMD-38465 Deposition: 27/12/2023
Map released: 30/10/2024
Last modified: 27/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-38465

Cryo-EM structure of human ZnT1 WT, in the absence of zinc, determined in an outward-facing conformation

EMD-38465

Single-particle
3.48 Å
EMD-38465 Deposition: 27/12/2023
Map released: 30/10/2024
Last modified: 27/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Zinc transporter 1
Fitted models: 8xm6 (Avg. Q-score: 0.435)

Deposition Authors: Qu Q , Long Y , Zhou Z
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
(2024) EMBO Rep , 25 , 5006 - 5025
PUBMED: 39390258
DOI: doi:10.1038/s44319-024-00287-3
ISSN: 1469-3178
Abstract:
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 Zn2+ translocation is coupled with H+ or Ca2+ 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 Zn2+ ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn2+ 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.