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Title | Cryo-EM structures of human ZnT8 in both outward- and inward-facing conformations. |
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Journal, issue, pages | Elife, Vol. 9, Year 2020 |
Publish date | Jul 29, 2020 |
![]() | Jing Xue / Tian Xie / Weizhong Zeng / Youxing Jiang / Xiao-Chen Bai / ![]() |
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 ...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. |
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Methods | EM (single particle) |
Resolution | 3.8 - 5.9 Å |
Structure data | EMDB-22285, PDB-6xpd: EMDB-22286, PDB-6xpe: EMDB-22287, PDB-6xpf: |
Chemicals | ![]() ChemComp-ZN: |
Source |
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![]() | TRANSPORT PROTEIN / ZnT8 / zinc transporter |