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TitleCryo-EM structure of the zinc-activated channel (ZAC) in the Cys-loop receptor superfamily.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 121, Issue 44, Page e2405659121, Year 2024
Publish dateOct 29, 2024
AuthorsFei Jin / Yi-Yu Lin / Ru-Chun Wang / Tang-Xuan Xie / Yimeng Zhao / Cheng Shen / Danqi Sheng / Muneyoshi Ichikawa / Ye Yu / Jin Wang / Motoyuki Hattori /
PubMed AbstractCys-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.
External linksProc Natl Acad Sci U S A / PubMed:39441630 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 3.6 Å
Structure data

37511

8wge

EMDB-37511, PDB-8wge:
Cryo-EM structure of the ZAC zinc-activated channel in the Cys-loop receptor superfamily
Method: EM (single particle) / Resolution: 3.4 Å

60471

8zts

EMDB-60471, PDB-8zts:
Cryo-EM structure of the ZAC zinc-activated channel in amphipol
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • oryzias latipes (Japanese medaka)
KeywordsTRANSPORT PROTEIN / Channel

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