6XPD

Cryo-EM structure of human ZnT8 double mutant - D110N and D224N, determined in outward-facing conformation

Summary for 6XPD

• Entry DOI: 10.2210/pdb6xpd/pdb
• EMDB information: 22285 22286 22287
• Descriptor: Zinc transporter 8, ZINC ION (2 entities in total)
• Functional Keywords: znt8, zinc transporter, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 70433.96

Authors

Bai, X.C.,Xue, J.,Jiang, Y.X. (deposition date: 2020-07-08, release date: 2020-08-05, Last modification date: 2024-03-06)

Primary citation

Xue, J.,Xie, T.,Zeng, W.,Jiang, Y.,Bai, X.C.
Cryo-EM structures of human ZnT8 in both outward- and inward-facing conformations.
Elife, 9:-, 2020

PubMed Abstract: ZnT8 is a Zn/H antiporter that belongs to SLC30 family and plays an essential role in regulating Zn accumulation in the insulin secretory granules of pancreatic β cells. However, the Zn/H exchange mechanism of ZnT8 remains unclear due to the lack of high-resolution structures. Here, we report the cryo-EM structures of human ZnT8 (HsZnT8) in both outward- and inward-facing conformations. HsZnT8 forms a dimeric structure with four Zn binding sites within each subunit: a highly conserved primary site in transmembrane domain (TMD) housing the Zn substrate; an interfacial site between TMD and C-terminal domain (CTD) that modulates the Zn transport activity of HsZnT8; and two adjacent sites buried in the cytosolic domain and chelated by conserved residues from CTD and the His-Cys-His (HCH) motif from the N-terminal segment of the neighboring subunit. A comparison of the outward- and inward-facing structures reveals that the TMD of each HsZnT8 subunit undergoes a large structural rearrangement, allowing for alternating access to the primary Zn site during the transport cycle. Collectively, our studies provide the structural insights into the Zn/H exchange mechanism of HsZnT8.

PubMed: 32723473
DOI: 10.7554/eLife.58823

Experimental method

ELECTRON MICROSCOPY (3.8 Å)