8f6z | pdb_00008f6z

Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with succinylcholine, desensitized-like state

spinqualitylabelsall models 8f6z, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8f6z is a 5 chain structure with sequence from Tetronarce californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.7Å Ligands: BMA, CLR, DD9, MAN, NAG, POV, SCK Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACHA_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 PubMed General anesthetics and neuromuscular blockers are used together during surgery to stabilize patients in an unconscious state. Anesthetics act mainly by potentiating inhibitory ion channels and inhibiting excitatory ion channels, with the net effect of dampening nervous system excitability. Neuromuscular blockers act by antagonizing nicotinic acetylcholine receptors at the motor endplate; these excitatory ligand-gated ion channels are also inhibited by general anesthetics. The mechanisms by which anesthetics and neuromuscular blockers inhibit nicotinic receptors are poorly understood but underlie safe and effective surgeries. Here we took a direct structural approach to define how a commonly used anesthetic and two neuromuscular blockers act on a muscle-type nicotinic receptor. We discover that the intravenous anesthetic etomidate binds at an intrasubunit site in the transmembrane domain and stabilizes a non-conducting, desensitized-like state of the channel. The depolarizing neuromuscular blocker succinylcholine also stabilizes a desensitized channel but does so through binding to the classical neurotransmitter site. Rocuronium binds in this same neurotransmitter site but locks the receptor in a resting, non-conducting state. Together, this study reveals a structural mechanism for how general anesthetics work on excitatory nicotinic receptors and further rationalizes clinical observations in how general anesthetics and neuromuscular blockers interact. Structural interplay of anesthetics and paralytics on muscle nicotinic receptors.,Goswami U, Rahman MM, Teng J, Hibbs RE Nat Commun. 2023 Jun 1;14(1):3169. doi: 10.1038/s41467-023-38827-5. PMID:37264005 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetyl choline receptor 3D structures

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