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.
journal_name
Neuronjournal_title
Neuronauthors
Rahman MM,Teng J,Worrell BT,Noviello CM,Lee M,Karlin A,Stowell MHB,Hibbs REdoi
10.1016/j.neuron.2020.03.012subject
Has Abstractpub_date
2020-06-17 00:00:00pages
952-962.e5issue
6eissn
0896-6273issn
1097-4199pii
S0896-6273(20)30219-1journal_volume
106pub_type
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