6UWZ

Cryo-EM structure of Torpedo acetylcholine receptor in complex with alpha-bungarotoxin

Summary for 6UWZ

• Entry DOI: 10.2210/pdb6uwz/pdb
• EMDB information: 20928
• Descriptor: Acetylcholine receptor subunit alpha, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-OCTANE, ... (12 entities in total)
• Functional Keywords: nicotinic acetylcholine receptor, nicotinic receptor, torpedo, cys-loop receptor, ion channel, neurotoxin, transport protein
• Biological source: Tetronarce californica (Pacific electric ray); More
• Total number of polymer chains: 7
• Total formula weight: 294424.71

Authors

Rahman, M.M.,Teng, J.,Worrell, B.T.,Noveillo, C.M.,Lee, M.,Karlin, A.,Stowell, M.,Hibbs, R.E. (deposition date: 2019-11-06, release date: 2020-04-15, Last modification date: 2020-07-29)

Primary citation

Rahman, M.M.,Teng, J.,Worrell, B.T.,Noviello, C.M.,Lee, M.,Karlin, A.,Stowell, M.H.B.,Hibbs, R.E.
Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins.
Neuron, 106:952-962.e5, 2020

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 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.

PubMed: 32275860
DOI: 10.1016/j.neuron.2020.03.012

Experimental method

ELECTRON MICROSCOPY (2.69 Å)