8XMA

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

Summary for 8XMA

• Entry DOI: 10.2210/pdb8xma/pdb
• EMDB information: 38469
• Descriptor: Proton-coupled zinc antiporter SLC30A1, ZINC ION, Lauryl Maltose Neopentyl Glycol, ... (4 entities in total)
• Functional Keywords: human znt1, zinc transpoter, outward-facing conformation, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 120591.66

Authors

Qu, Q.,Long, Y.,Zhou, Z. (deposition date: 2023-12-27, release date: 2024-10-30, Last modification date: 2024-11-27)

Primary citation

Long, Y.,Zhu, Z.,Zhou, Z.,Yang, C.,Chao, Y.,Wang, Y.,Zhou, Q.,Wang, M.W.,Qu, Q.
Structural insights into human zinc transporter ZnT1 mediated Zn 2+ efflux.
Embo Rep., 25:5006-5025, 2024

PubMed 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 Zn translocation is coupled with H or Ca 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 Zn ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn 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.

PubMed: 39390258
DOI: 10.1038/s44319-024-00287-3

Experimental method

ELECTRON MICROSCOPY (2.65 Å)