EMD-25207

Single-particle
3.18 Å
EMD-25207 Deposition: 26/10/2021
Map released: 09/03/2022
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-25207

Cryo-EM structure of Torpedo acetylcholine receptor in complex with d-tubocurarine

EMD-25207

Single-particle
3.18 Å
EMD-25207 Deposition: 26/10/2021
Map released: 09/03/2022
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Tetronarce californica
Sample: Torpedo acetylcholine receptor in complex with d-tubocurarine
Fitted models: 7sms (Avg. Q-score: 0.544)

Deposition Authors: Rahman MM , Basta T
Structural mechanism of muscle nicotinic receptor desensitization and block by curare.
Rahman MM , Basta T, Teng J, Lee M, Worrell BT, Stowell MHB , Hibbs RE
(2022) Nat Struct Mol Biol , 29 , 386 - 394
PUBMED: 35301478
DOI: doi:10.1038/s41594-022-00737-3
ISSN: 1545-9985
Abstract:
Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of three-dimensional structure how agonists and antagonists alter nicotinic acetylcholine receptor conformation. We used the muscle-type receptor from the Torpedo ray to first define the structure of the receptor in a resting, activatable state. We then determined the receptor structure bound to the agonist carbachol, which stabilizes an asymmetric, closed channel desensitized state. We find conformational changes in a peripheral membrane helix are tied to recovery from desensitization. To probe mechanisms of antagonism, we obtained receptor structures with the active component of curare, a poison arrow toxin and precursor to modern muscle relaxants. d-Tubocurarine stabilizes the receptor in a desensitized-like state in the presence and absence of agonist. These findings define the transitions between resting and desensitized states and reveal divergent means by which antagonists block channel activity of the muscle-type nicotinic receptor.