Structural basis of human zinc-activated channel (ZAC) signaling and modulation
ions bind to the subunit interfaces of the extracellular domain, corresponding to the canonical agonist-binding sites in the classical CLRs, and are primarily coordinated through cation‒π interactions with two aromatic residues. While the antagonist TTFB inhibits ZAC by insertion between the transmembrane M2 helices of adjacent subunits, d-tubocurarine acts in a dual manner by blocking the channel and interfering with agonist binding. Combined with mutagenesis and electrophysiological analysis, these evaluations highlight the distinctive structural and functional features of this atypical CLR.
Authors
- Qianhui Qu (ORCID: https://orcid.org/0000-0002-5753-2599)
- Yulin Chao (ORCID: https://orcid.org/0009-0005-2230-1167)
- Zixuan Zhou (ORCID: https://orcid.org/0000-0002-2432-4283)
- Yonghui Long (ORCID: https://orcid.org/0000-0001-6412-8415)
- Yilai Shu
- Anders Jensen
- Chuanhui Yang
- Hongtao Zhu
Institutions
- University of Copenhagen (DK)
- Fudan University (CN)
- Eye & ENT Hospital of Fudan University (CN)
- FZU ‒ Institute of Physics of the Academy of Sciences of the Czech Republic (CZ)
- Ministry of Science and Technology (LA)
- State Key Laboratory of Medical Neurobiology
Publication Details
- Journal
- Cell Discovery
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1038/s41421-026-00878-5
- Primary Topic
- Nicotinic Acetylcholine Receptors Study
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Fudan University
- Lundbeckfonden
- Danmarks Frie Forskningsfond
- H. Lundbeck A/S
- National Science and Technology Major Project
- Shanghai Medical College, Fudan University