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Publication Abstract from PubMed

Zinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet beta cells and is responsible for H(+)-coupled uptake (antiport) of Zn(2+) 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(2+). 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(2+) at a luminal pH (5.5). Compared to a Zn(2+)-bound xtZnT8 structure at a cytosolic pH (7.5), the low-pH structure displays an empty transmembrane Zn(2+)-binding site with a disrupted coordination geometry. Combined with a Zn(2+)-binding assay our data suggest that protons may disrupt Zn(2+) coordination at the transmembrane Zn(2+)-binding site in the lumen-facing state, thus facilitating Zn(2+) release from ZnT8 into the lumen.

Cryo-EM structure of a eukaryotic zinc transporter at a low pH suggests its Zn(2+)-releasing mechanism.,Zhang S, Fu C, Luo Y, Xie Q, Xu T, Sun Z, Su Z, Zhou X J Struct Biol. 2022 Dec 1;215(1):107926. doi: 10.1016/j.jsb.2022.107926. PMID:36464198^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.