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Open data
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Basic information
Entry | Database: PDB / ID: 7m6n | |||||||||
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Title | Full length alpha1 Glycine receptor in presence of 0.1mM Glycine | |||||||||
![]() | Glycine receptor subunit alphaZ1 | |||||||||
![]() | MEMBRANE PROTEIN / Ions Ligands Receptors / Glycine receptor Recombinant Proteins | |||||||||
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 / central nervous system development / cellular response to amino acid stimulus / transmembrane signaling receptor activity / postsynaptic membrane / perikaryon / neuron projection / synapse / dendrite / zinc ion binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.61 Å | |||||||||
![]() | Kumar, A. / Chakrapani, S. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs. Authors: Arvind Kumar / Kayla Kindig / Shanlin Rao / Afroditi-Maria Zaki / Sandip Basak / Mark S P Sansom / Philip C Biggin / Sudha Chakrapani / ![]() ![]() Abstract: Nociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain ...Nociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain and in the treatment of several neurological disorders. High-resolution mechanistic details of GlyR function and its modulation are just emerging. While it has been known that cannabinoids such as Δ-tetrahydrocannabinol (THC), the principal psychoactive constituent in marijuana, potentiate GlyR in the therapeutically relevant concentration range, the molecular mechanism underlying this effect is still not understood. Here, we present Cryo-EM structures of full-length GlyR reconstituted into lipid nanodisc in complex with THC under varying concentrations of glycine. The GlyR-THC complexes are captured in multiple conformational states that reveal the basis for THC-mediated potentiation, manifested as different extents of opening at the level of the channel pore. Taken together, these structural findings, combined with molecular dynamics simulations and functional analysis, provide insights into the potential THC binding site and the allosteric coupling to the channel pore. #1: ![]() 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. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 322.8 KB | Display | ![]() |
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PDB format | ![]() | 267.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 23701MC ![]() 7m6mC ![]() 7m6oC ![]() 7m6pC ![]() 7m6qC ![]() 7m6rC ![]() 7m6sC 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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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 50821.711 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #2: Chemical | ChemComp-GLY / #3: Sugar | ChemComp-NAG / 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: Glycine receptor subunit alpha Z1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 250 kDa/nm / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: ![]() ![]() | |||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES 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 |
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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 magnification: 130000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
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: GIF Bioquantum / Energyfilter slit width: 20 eV |
Image scans | Movie frames/image: 40 |
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Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.61 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 89791 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Highest resolution: 2.61 Å | ||||||||||||||||||||||||
Refine LS restraints |
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