Journal
NEURON
Volume 106, Issue 6, Pages 952-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2020.03.012
Keywords
-
Categories
Funding
- CPRIT Core Facility Support Award [RP170644]
- NIH [DA037492, DA042072, NS095899, AG061829, U24GM129547]
- Office of Biological and Environmental Research [grid.436923.9]
- MCDB Neurodegenerative Disease Fund
Ask authors/readers for more resources
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 alpha-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 similar to 60 angstrom 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available