8ZTS

Cryo-EM structure of the ZAC zinc-activated channel in amphipol

Summary for 8ZTS

• Entry DOI: 10.2210/pdb8zts/pdb
• EMDB information: 60471
• Descriptor: ZAC, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: transport protein
• Biological source: Oryzias latipes
• Total number of polymer chains: 5
• Total formula weight: 237385.32

Authors

Jin, F.,Hattori, M. (deposition date: 2024-06-07, release date: 2024-11-27, Last modification date: 2025-06-25)

Primary citation

Jin, F.,Lin, Y.Y.,Wang, R.C.,Xie, T.X.,Zhao, Y.,Shen, C.,Sheng, D.,Ichikawa, M.,Yu, Y.,Wang, J.,Hattori, M.
Cryo-EM structure of the zinc-activated channel (ZAC) in the Cys-loop receptor superfamily.
Proc.Natl.Acad.Sci.USA, 121:e2405659121-e2405659121, 2024

PubMed Abstract: 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.

PubMed: 39441630
DOI: 10.1073/pnas.2405659121

Experimental method

ELECTRON MICROSCOPY (3.6 Å)