National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2024 タイトル: Cryo-EM structure of the zinc-activated channel (ZAC) in the Cys-loop receptor superfamily. 著者: Fei Jin / Yi-Yu Lin / Ru-Chun Wang / Tang-Xuan Xie / Yimeng Zhao / Cheng Shen / Danqi Sheng / Muneyoshi Ichikawa / Ye Yu / Jin Wang / Motoyuki Hattori / 要旨: Cys-loop receptors are a large superfamily of pentameric ligand-gated ion channels with various physiological roles, especially in neurotransmission in the central nervous system. Among them, zinc- ...Cys-loop receptors are a large superfamily of pentameric ligand-gated ion channels with various physiological roles, especially in neurotransmission in the central nervous system. Among them, zinc-activated channel (ZAC) is a Zn-activated ion channel that is widely expressed in the human body and is conserved among eukaryotes. Due to its gating by extracellular Zn, ZAC has been considered a Zn sensor, but it has undergone minimal structural and functional characterization since its molecular cloning. Among the families in the Cys-loop receptor superfamily, only the structure of ZAC has yet to be determined. Here, we determined the cryo-EM structure of ZAC in the apo state and performed structure-based mutation analyses. We identified a few residues in the extracellular domain whose mutations had a mild impact on Zn sensitivity. The constriction site in the ion-conducting pore differs from the one in other Cys-loop receptor structures, and further mutational analysis identified a key residue that is important for ion selectivity. In summary, our work provides a structural framework for understanding the ion-conducting mechanism of ZAC.