7smr
From Proteopedia
Cryo-EM structure of Torpedo acetylcholine receptor in complex with carbachol, desensitized state
Structural highlights
FunctionACHA_TETCF After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. Publication Abstract from PubMedBinding 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. 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 Nat Struct Mol Biol. 2022 Apr;29(4):386-394. doi: 10.1038/s41594-022-00737-3. , Epub 2022 Mar 17. PMID:35301478[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Tetronarce californica | Basta T | Hibbs RE | Lee M | Rahman MM | Stowell MHB | Teng J | Worrell BT
