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- EMDB-6346: Structure of alpha-1 glycine receptor by single particle electron... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-6346 | |||||||||
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Title | Structure of alpha-1 glycine receptor by single particle electron cryo-microscopy, glycine/ivermectin-bound state | |||||||||
![]() | Reconstruction of zebra fish alpha1 glycine receptor bound with glycine/ivermectin | |||||||||
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![]() | activation / inhibition / modulation / cys loop receptor / glycine / strychnine / ivermectin | |||||||||
Function / homology | ![]() Neurotransmitter receptors and postsynaptic signal transmission / transmitter-gated monoatomic ion channel activity / extracellularly glycine-gated ion channel activity / extracellularly glycine-gated chloride channel activity / cellular response to ethanol / cellular response to zinc ion / regulation of neuron differentiation / neurotransmitter receptor activity / glycine binding / chloride channel complex ...Neurotransmitter receptors and postsynaptic signal transmission / transmitter-gated monoatomic ion channel activity / extracellularly glycine-gated ion channel activity / extracellularly glycine-gated chloride channel activity / cellular response to ethanol / cellular response to zinc ion / regulation of neuron differentiation / neurotransmitter receptor activity / glycine binding / chloride channel complex / ligand-gated monoatomic ion channel activity / transmembrane transporter complex / response to amino acid / monoatomic ion transport / chloride transmembrane transport / cellular response to amino acid stimulus / central nervous system development / transmembrane signaling receptor activity / postsynaptic membrane / perikaryon / neuron projection / synapse / dendrite / zinc ion binding / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Du J / Lu W / Wu SP / Cheng YF / Gouaux E | |||||||||
![]() | ![]() Title: Glycine receptor mechanism elucidated by electron cryo-microscopy. Authors: Juan Du / Wei Lü / Shenping Wu / Yifan Cheng / Eric Gouaux / ![]() Abstract: The strychnine-sensitive glycine receptor (GlyR) mediates inhibitory synaptic transmission in the spinal cord and brainstem and is linked to neurological disorders, including autism and hyperekplexia. ...The strychnine-sensitive glycine receptor (GlyR) mediates inhibitory synaptic transmission in the spinal cord and brainstem and is linked to neurological disorders, including autism and hyperekplexia. Understanding of molecular mechanisms and pharmacology of glycine receptors has been hindered by a lack of high-resolution structures. Here we report electron cryo-microscopy structures of the zebrafish α1 GlyR with strychnine, glycine, or glycine and ivermectin (glycine/ivermectin). Strychnine arrests the receptor in an antagonist-bound closed ion channel state, glycine stabilizes the receptor in an agonist-bound open channel state, and the glycine/ivermectin complex adopts a potentially desensitized or partially open state. Relative to the glycine-bound state, strychnine expands the agonist-binding pocket via outward movement of the C loop, promotes rearrangement of the extracellular and transmembrane domain 'wrist' interface, and leads to rotation of the transmembrane domain towards the pore axis, occluding the ion conduction pathway. These structures illuminate the GlyR mechanism and define a rubric to interpret structures of Cys-loop receptors. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 65.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.3 KB 11.3 KB | Display Display | ![]() |
Images | ![]() ![]() | 70 KB 4.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 379.3 KB | Display | ![]() |
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Full document | ![]() | 378.9 KB | Display | |
Data in XML | ![]() | 6.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 3jafMC ![]() 6344C ![]() 6345C ![]() 3jadC ![]() 3jaeC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Reconstruction of zebra fish alpha1 glycine receptor bound with glycine/ivermectin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Zebra fish alpha-1 glycine receptor bound with glycine/ivermectin
Entire | Name: Zebra fish alpha-1 glycine receptor bound with glycine/ivermectin |
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Components |
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-Supramolecule #1000: Zebra fish alpha-1 glycine receptor bound with glycine/ivermectin
Supramolecule | Name: Zebra fish alpha-1 glycine receptor bound with glycine/ivermectin type: sample / ID: 1000 / Oligomeric state: pentamer / Number unique components: 1 |
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Molecular weight | Experimental: 200 KDa / Theoretical: 200 KDa |
-Macromolecule #1: alpha1 glycine receptor
Macromolecule | Name: alpha1 glycine receptor / type: protein_or_peptide / ID: 1 / Name.synonym: alpha1 GlyR / Number of copies: 1 / Oligomeric state: pentamer / Recombinant expression: Yes |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Experimental: 200 KDa / Theoretical: 200 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | UniProtKB: Glycine receptor, alpha 1 / InterPro: Glycine receptor alpha1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3.3 mg/mL |
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Buffer | pH: 8 Details: 150 mM NaCl, 20 mM Tris-HCl, 1 mM C12M, 10 mM glycine, 5 uM ivermectin |
Grid | Details: 200 mesh copper 1.2/1.3 Quantifoil carbon grid |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 90 K / Instrument: FEI VITROBOT MARK III / Method: Blot for 3.5 seconds before plunging. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: Gatan |
Date | Oct 6, 2014 |
Image recording | Category: CCD / Film or detector model: GATAN K2 (4k x 4k) / Number real images: 2489 / Average electron dose: 46 e/Å2 Details: Gatan K2 Summit in super-resolution counting mode. Motion correction as described in Li et al. (2013) Nature Methods. |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.01 mm / Nominal defocus max: -3.0 µm / Nominal defocus min: -1.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Details | Movies were aligned using motioncorr. Image processing was done using Relion. |
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CTF correction | Details: each particle |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: OTHER / Software - Name: Relion Details: Particle picking, 2D classification, 3D classification, refinement, and reconstruction were done using Relion. Number images used: 56957 |
-Atomic model buiding 1
Initial model | PDB ID: Chain - #0 - Chain ID: A / Chain - #1 - Chain ID: B / Chain - #2 - Chain ID: C / Chain - #3 - Chain ID: D / Chain - #4 - Chain ID: E |
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Software | Name: ![]() |
Details | The model (3RHW) was fit into the density map using UCSF Chimera. Further de novo model building was done using COOT. |
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
Output model | ![]() PDB-3jaf: |