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- PDB-8esk: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8esk | ||||||
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Title | Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with rocuronium, resting-like state | ||||||
![]() | (Acetylcholine receptor subunit ...) x 4 | ||||||
![]() | TRANSPORT PROTEIN/INHIBITOR / acetylcholine receptor / nicotinic receptor / Torpedo / Cys-loop receptor / ion channel / muscle-type nicotinic receptor / TRANSPORT PROTEIN-INHIBITOR complex / Neuromuscular Blocker / Inhibitor | ||||||
Function / homology | ![]() acetylcholine-gated monoatomic cation-selective channel activity / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / transmembrane signaling receptor activity / postsynaptic membrane / neuron projection Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
![]() | Goswami, U. / Rahman, M.M. / Teng, J. / Hibbs, R.E. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural interplay of anesthetics and paralytics on muscle nicotinic receptors. Authors: Umang Goswami / Md Mahfuzur Rahman / Jinfeng Teng / Ryan E Hibbs / ![]() Abstract: 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 ...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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 802.9 KB | Display | ![]() |
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PDB format | ![]() | 684.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 28576MC ![]() 8f2sC ![]() 8f6yC ![]() 8f6zC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Acetylcholine receptor subunit ... , 4 types, 5 molecules ADBCE
#1: Protein | Mass: 50168.164 Da / Num. of mol.: 2 / Source method: isolated from a natural source Source: (natural) ![]() ![]() References: UniProt: P02710 #2: Protein | | Mass: 57625.711 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() References: UniProt: P02718 #3: Protein | | Mass: 53731.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() References: UniProt: P02712 #4: Protein | | Mass: 56335.684 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() ![]() References: UniProt: P02714 |
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-Sugars , 5 types, 8 molecules ![](data/chem/img/NAG.gif)
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #7: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #8: Polysaccharide | alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #12: Sugar | |
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-Non-polymers , 3 types, 13 molecules ![](data/chem/img/RBR.gif)
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#9: Chemical | #10: Chemical | ChemComp-POV / ( #11: Chemical | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with rocuronium, resting-like state Type: COMPLEX / Entity ID: #1-#4 / Source: NATURAL |
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Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 500 nm / Nominal defocus min: 2500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 146932 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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