Abstract
The nicotinic acetylcholine receptor, a pentameric ligand-gated ion channel, converts the free energy of binding of the neurotransmitter acetylcholine into opening of its central pore. Here we present the first high-resolution structure of the receptor type found in muscle-endplate membrane and in the muscle-derived electric tissues of fish. The native receptor was purified from Torpedo electric tissue and functionally reconstituted in lipids optimal for cryo-electron microscopy. The receptor was stabilized in a closed state by the binding of α-bungarotoxin. The structure reveals the binding of a toxin molecule at each of two subunit interfaces in a manner that would block the binding of acetylcholine. It also reveals a closed gate in the ion-conducting pore, formed by hydrophobic amino acid side chains, located ∼60 Å from the toxin binding sites. The structure provides a framework for understanding gating in ligand-gated channels and how mutations in the acetylcholine receptor cause congenital myasthenic syndromes. Rahman et al. report the high-resolution single-particle cryo-EM structure of a native muscle-type nicotinic acetylcholine receptor from the Torpedo electric ray, in complex with α-bungarotoxin from the banded krait. The structure was obtained in a lipidic environment shown to support channel function and reveals a closed, hydrophobic ion channel gate.
Original language | English (US) |
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Pages (from-to) | 952-962.e5 |
Journal | Neuron |
Volume | 106 |
Issue number | 6 |
DOIs | |
State | Published - Jun 17 2020 |
Keywords
- Cys-loop receptor
- Torpedo
- acetylcholine receptor
- cryo-EM
- ion channel structure
- ligand-gated ion channel
- membrane protein
- nicotinic receptor
- toxin
- α-bungarotoxin
ASJC Scopus subject areas
- General Neuroscience