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| Title | Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins. |
|---|---|
| Journal, issue, pages | Neuron, Vol. 106, Issue 6, Page 952-962.e5, Year 2020 |
| Publish date | Jun 17, 2020 |
Authors | Md Mahfuzur Rahman / Jinfeng Teng / Brady T Worrell / Colleen M Noviello / Myeongseon Lee / Arthur Karlin / Michael H B Stowell / Ryan E Hibbs / ![]() |
| PubMed 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 ...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. |
External links | Neuron / PubMed:32275860 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.69 Å |
| Structure data | EMDB-20928, PDB-6uwz: |
| Chemicals | ![]() ChemComp-POV: ![]() ChemComp-NAG: ![]() ChemComp-OCT: ![]() ChemComp-HOH: |
| Source |
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Keywords | TRANSPORT PROTEIN / Nicotinic acetylcholine receptor / nicotinic receptor / Torpedo / Cys-loop receptor / ion channel / neurotoxin |
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bungarus multicinctus (many-banded krait)
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