Cryo-EM structures of human ZnT8 in both outward- and inward-facing conformations.

ABSTRACT: ZnT8 is a Zn²⁺/H⁺ antiporter that belongs to SLC30 family and plays an essential role in regulating Zn²⁺ accumulation in the insulin secretory granules of pancreatic β cells. However, the Zn²⁺/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 Zn²⁺ binding sites within each subunit: a highly conserved primary site in transmembrane domain (TMD) housing the Zn²⁺ substrate; an interfacial site between TMD and C-terminal domain (CTD) that modulates the Zn²⁺ transport activity of HsZnT8; and two adjacent sites buri

SUBMITTER: Xue J 

PROVIDER: S-EPMC7428307 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature