7QL5

Torpedo muscle-type nicotinic acetylcholine receptor - nicotine-bound conformation

Summary for 7QL5

• Entry DOI: 10.2210/pdb7ql5/pdb
• Related: 7QKO
• EMDB information: 14064
• Descriptor: Acetylcholine receptor subunit alpha, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• Functional Keywords: pentameric ligand-gated ion channel, nicotinic receptor, membrane protein
• Biological source: Tetronarce californica (Pacific electric ray); More
• Total number of polymer chains: 5
• Total formula weight: 283473.91

Authors

Zarkadas, E.,Pebay-Peyroula, E.,Baenziger, J.,Nury, H. (deposition date: 2021-12-19, release date: 2022-02-09, Last modification date: 2024-11-13)

Primary citation

Zarkadas, E.,Pebay-Peyroula, E.,Thompson, M.J.,Schoehn, G.,Uchanski, T.,Steyaert, J.,Chipot, C.,Dehez, F.,Baenziger, J.E.,Nury, H.
Conformational transitions and ligand-binding to a muscle-type nicotinic acetylcholine receptor.
Neuron, 110:1358-, 2022

PubMed Abstract: Fast synaptic communication requires receptors that respond to the presence of neurotransmitter by opening an ion channel across the post-synaptic membrane. The muscle-type nicotinic acetylcholine receptor from the electric fish, Torpedo, is the prototypic ligand-gated ion channel, yet the structural changes underlying channel activation remain undefined. Here we use cryo-EM to solve apo and agonist-bound structures of the Torpedo nicotinic receptor embedded in a lipid nanodisc. Using both a direct biochemical assay to define the conformational landscape and molecular dynamics simulations to assay flux through the pore, we correlate structures with functional states and elucidate the motions that lead to pore activation of a heteromeric nicotinic receptor. We highlight an underappreciated role for the complementary subunit in channel gating, establish the structural basis for the differential agonist affinities of α/δ versus α /γ sites, and explain why nicotine is less potent at muscle nicotinic receptors compared to neuronal ones.

PubMed: 35139364
DOI: 10.1016/j.neuron.2022.01.013

Experimental method

ELECTRON MICROSCOPY (2.5 Å)