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TitleCryo-EM structure of a eukaryotic zinc transporter at a low pH suggests its Zn-releasing mechanism.
Journal, issue, pagesJ Struct Biol, Vol. 215, Issue 1, Page 107926, Year 2023
Publish dateDec 1, 2022
AuthorsSenfeng Zhang / Chunting Fu / Yongbo Luo / Qingrong Xie / Tong Xu / Ziyi Sun / Zhaoming Su / Xiaoming Zhou /
PubMed AbstractZinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet β cells and is responsible for H-coupled uptake (antiport) of Zn into the lumen of insulin secretory granules. Structures of human ...Zinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet β cells and is responsible for H-coupled uptake (antiport) of Zn into the lumen of insulin secretory granules. Structures of human ZnT8 and its prokaryotic homolog YiiP have provided structural basis for constructing a plausible transport cycle for Zn. However, the mechanistic role that protons play in the transport process remains unclear. Here we present a lumen-facing cryo-EM structure of ZnT8 from Xenopus tropicalis (xtZnT8) in the presence of Zn at a luminal pH (5.5). Compared to a Zn-bound xtZnT8 structure at a cytosolic pH (7.5), the low-pH structure displays an empty transmembrane Zn-binding site with a disrupted coordination geometry. Combined with a Zn-binding assay our data suggest that protons may disrupt Zn coordination at the transmembrane Zn-binding site in the lumen-facing state, thus facilitating Zn release from ZnT8 into the lumen.
External linksJ Struct Biol / PubMed:36464198
MethodsEM (single particle)
Resolution3.72 - 3.85 Å
Structure data

33619

7y5g

EMDB-33619, PDB-7y5g:
Cryo-EM structure of a eukaryotic ZnT8 in the presence of zinc
Method: EM (single particle) / Resolution: 3.85 Å

33620

7y5h

EMDB-33620, PDB-7y5h:
Cryo-EM structure of a eukaryotic ZnT8 at a low pH
Method: EM (single particle) / Resolution: 3.72 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • xenopus tropicalis (tropical clawed frog)
KeywordsMEMBRANE PROTEIN / Zinc transporter / SLC30 / ZnT / CDF / Proton-coupled antiporter

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