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| Title | Asynchronous subunit transitions prime acetylcholine receptor activation. |
|---|---|
| Journal, issue, pages | Science, Vol. 391, Issue 6780, Page eadw1264, Year 2026 |
| Publish date | Jan 1, 2026 |
Authors | Mackenzie J Thompson / Christian J G Tessier / Anna Ananchenko / Camille Hénault / Johnathon R Emlaw / François Dehez / Eleftherios Zarkadas / Corrie J B daCosta / Hugues Nury / John E Baenziger / ![]() |
| PubMed Abstract | Communication at synapses is facilitated by postsynaptic receptors, which convert a chemical signal into an electrical response. For ligand-gated ion channels, agonist binding triggers rapid ...Communication at synapses is facilitated by postsynaptic receptors, which convert a chemical signal into an electrical response. For ligand-gated ion channels, agonist binding triggers rapid transitions through intermediate states leading to a transient open-pore conformation, with these transitions shaping the postsynaptic response. In this work, we determine structures of the muscle-type nicotinic acetylcholine receptor in unliganded, mono-liganded, and di-liganded states. Agonist binding to a single site stabilizes a closed structure where an entire principal agonist-binding subunit transitions to an active-like conformation, whereas the other unoccupied principal subunit remains inactive, albeit poised for activation. Uniting this intermediate structure with single-channel recordings informs a sequential activation mechanism where asynchronous subunit transitions prime the receptor for activation-a finding with implications for an entire superfamily of pentameric ligand-gated ion channels. |
External links | Science / PubMed:41037590 |
| Methods | EM (single particle) |
| Resolution | 2.8 - 3.2 Å |
| Structure data | EMDB-47480, PDB-9e3e: EMDB-47481, PDB-9e3f: EMDB-47482, PDB-9e3g: |
| Chemicals | ![]() ChemComp-ACH: ![]() ChemComp-POV: |
| Source |
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Keywords | MEMBRANE PROTEIN / Nicotinic acetylcholine receptor / Ion channel / Cys-loop receptor / Pentameric ligand-gated ion channel / Neurotransmitter-gated receptor / Ligand-gated ion channel / Primed state |
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