[English] 日本語
![](img/lk-miru.gif)
- PDB-6vm0: Full length Glycine receptor reconstituted in lipid nanodisc in G... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6vm0 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Full length Glycine receptor reconstituted in lipid nanodisc in Gly/IVM-conformation (State-1) | |||||||||
![]() | Glycine receptor subunit alphaZ1![]() | |||||||||
![]() | ![]() | |||||||||
Function / homology | ![]() Neurotransmitter receptors and postsynaptic signal transmission / extracellularly glycine-gated ion channel activity / extracellularly glycine-gated chloride channel activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Kumar, A. / Basak, S. / Chakrapani, S. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs. Authors: Arvind Kumar / Sandip Basak / Shanlin Rao / Yvonne Gicheru / Megan L Mayer / Mark S P Sansom / Sudha Chakrapani / ![]() ![]() Abstract: Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyRs) are key players in mediating fast inhibitory neurotransmission ...Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyRs) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structures have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unanswered. Here, we present Cryo-EM structures of the full-length GlyR protein complex reconstituted into lipid nanodiscs that are captured in the unliganded (closed), glycine-bound (open and desensitized), and allosteric modulator-bound conformations. A comparison of these states reveals global conformational changes underlying GlyR channel gating and modulation. The functional state assignments were validated by molecular dynamics simulations, and the observed permeation events are in agreement with the anion selectivity and conductance of GlyR. These studies provide the structural basis for gating, ion selectivity, and single-channel conductance properties of GlyR in a lipid environment. #1: ![]() 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 |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 342.4 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 281.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 21234MC ![]() 6ubsC ![]() 6ubtC ![]() 6ud3C ![]() 6vm2C ![]() 6vm3C M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | ![]() Mass: 50821.711 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #2: 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 #3: Chemical | ChemComp-PIO / [( #4: Chemical | ChemComp-GLY / ![]() #5: Chemical | ChemComp-IVM / ( ![]() Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component | Name: Glycine receptor subunit alpha Z1![]() | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 250 kDa/nm / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: ![]() ![]() ![]() | |||||||||||||||
Source (recombinant) | Organism: ![]() ![]() ![]() | |||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||
Buffer component |
| |||||||||||||||
Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() Details: Full length Zebrafish GlyR alpha1 homopentamer reconsituted in Nanodisc | |||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 4 K Details: 3.5 ul of 0.1 mg/ml protein solution was applied on a grid in the Vitrobot MkIV chamber set to 100% RH at 4 degC for 30s and then blotted for 2 s and plunged |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 9 sec. / Electron dose: 40 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 8 / Num. of real images: 9700 |
EM imaging optics | Energyfilter name![]() |
Image scans | Movie frames/image: 40 |
-
Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry![]() ![]() | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.14 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 19600 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|