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Yorodumi- PDB-7z14: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in ... -
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-Basic information
Entry | Database: PDB / ID: 7z14 | |||||||||||||||||||||
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Title | Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with a short-chain neurotoxin. | |||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Ion channel / toxin | |||||||||||||||||||||
Function / homology | Function and homology information 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 | synthetic construct (others) Tetronarce californica (Pacific electric ray) | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.15 Å | |||||||||||||||||||||
Authors | Nys, M.A.E.M. / Zarkadas, E. / Ulens, C. / Nury, H. | |||||||||||||||||||||
Funding support | Belgium, United Kingdom, France, European Union, 6items
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Citation | Journal: Nat Commun / Year: 2022 Title: The molecular mechanism of snake short-chain α-neurotoxin binding to muscle-type nicotinic acetylcholine receptors. Authors: Mieke Nys / Eleftherios Zarkadas / Marijke Brams / Aujan Mehregan / Kumiko Kambara / Jeroen Kool / Nicholas R Casewell / Daniel Bertrand / John E Baenziger / Hugues Nury / Chris Ulens / Abstract: Bites by elapid snakes (e.g. cobras) can result in life-threatening paralysis caused by venom neurotoxins blocking neuromuscular nicotinic acetylcholine receptors. Here, we determine the cryo-EM ...Bites by elapid snakes (e.g. cobras) can result in life-threatening paralysis caused by venom neurotoxins blocking neuromuscular nicotinic acetylcholine receptors. Here, we determine the cryo-EM structure of the muscle-type Torpedo receptor in complex with ScNtx, a recombinant short-chain α-neurotoxin. ScNtx is pinched between loop C on the principal subunit and a unique hairpin in loop F on the complementary subunit, thereby blocking access to the neurotransmitter binding site. ScNtx adopts a binding mode that is tilted toward the complementary subunit, forming a wider network of interactions than those seen in the long-chain α-Bungarotoxin complex. Certain mutations in ScNtx at the toxin-receptor interface eliminate inhibition of neuronal α7 nAChRs, but not of human muscle-type receptors. These observations explain why ScNtx binds more tightly to muscle-type receptors than neuronal receptors. Together, these data offer a framework for understanding subtype-specific actions of short-chain α-neurotoxins and inspire strategies for design of new snake antivenoms. | |||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7z14.cif.gz | 360.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7z14.ent.gz | 291.7 KB | Display | PDB format |
PDBx/mmJSON format | 7z14.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7z14_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7z14_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7z14_validation.xml.gz | 50.2 KB | Display | |
Data in CIF | 7z14_validation.cif.gz | 72.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z1/7z14 ftp://data.pdbj.org/pub/pdb/validation_reports/z1/7z14 | HTTPS FTP |
-Related structure data
Related structure data | 14440MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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) Tetronarce californica (Pacific electric ray) References: UniProt: P02710 #2: Protein | | Mass: 53731.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Tetronarce californica (Pacific electric ray) References: UniProt: P02712 #3: Protein | | Mass: 57625.711 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Tetronarce californica (Pacific electric ray) References: UniProt: P02718 #4: Protein | | Mass: 56335.684 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Tetronarce californica (Pacific electric ray) References: UniProt: P02714 |
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-Protein , 1 types, 2 molecules FG
#5: Protein | Mass: 6848.960 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Consensus sequence from Elapidae family (8602) / Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) Strain (production host): E. coli K-12 derived Origami 2 cells |
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-Sugars , 4 types, 6 molecules
#6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Type: oligosaccharide / Mass: 951.875 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source #9: Sugar | ChemComp-NAG / | |
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-Details
Has ligand of interest | N |
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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 |
-Sample preparation
Component | Name: Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with a short-chain neurotoxin. Type: COMPLEX / Entity ID: #1, #3, #2, #4-#5 / Source: MULTIPLE SOURCES |
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Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.15 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26581 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 89.67 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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