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Yorodumi- PDB-9b36: Open state of kainate receptor GluK2 in complex with agonist glut... -
+Open data
-Basic information
Entry | Database: PDB / ID: 9b36 | |||||||||||||||
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Title | Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two concanavalin A dimers. Composite map. | |||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / kainate receptor / GluK2 / positive allosteric modulator / BPAM344 / open / concanavalin A / ConA / glutamate | |||||||||||||||
Function / homology | Function and homology information mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / D-glucose binding / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity ...mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / D-glucose binding / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity / ubiquitin conjugating enzyme binding / receptor clustering / modulation of excitatory postsynaptic potential / extracellularly glutamate-gated ion channel activity / D-mannose binding / regulation of JNK cascade / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / behavioral fear response / neuronal action potential / positive regulation of synaptic transmission / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic modulation of chemical synaptic transmission / dendrite cytoplasm / hippocampal mossy fiber to CA3 synapse / regulation of membrane potential / SNARE binding / excitatory postsynaptic potential / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / modulation of chemical synaptic transmission / terminal bouton / intracellular calcium ion homeostasis / vasodilation / positive regulation of neuron apoptotic process / manganese ion binding / presynaptic membrane / scaffold protein binding / chemical synaptic transmission / perikaryon / postsynaptic membrane / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynaptic density / axon / neuronal cell body / glutamatergic synapse / dendrite / ubiquitin protein ligase binding / calcium ion binding / synapse / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | Rattus norvegicus (Norway rat) Canavalia ensiformis (jack bean) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.29 Å | |||||||||||||||
Authors | Nadezhdin, K.D. / Gangwar, S.P. / Sobolevsky, A.I. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Nature / Year: 2024 Title: Kainate receptor channel opening and gating mechanism. Authors: Shanti Pal Gangwar / Maria V Yelshanskaya / Kirill D Nadezhdin / Laura Y Yen / Thomas P Newton / Muhammed Aktolun / Maria G Kurnikova / Alexander I Sobolevsky / Abstract: Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and ...Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9b36.cif.gz | 799.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9b36.ent.gz | 669.6 KB | Display | PDB format |
PDBx/mmJSON format | 9b36.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9b36_validation.pdf.gz | 3.5 MB | Display | wwPDB validaton report |
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Full document | 9b36_full_validation.pdf.gz | 3.6 MB | Display | |
Data in XML | 9b36_validation.xml.gz | 125.5 KB | Display | |
Data in CIF | 9b36_validation.cif.gz | 182.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b3/9b36 ftp://data.pdbj.org/pub/pdb/validation_reports/b3/9b36 | HTTPS FTP |
-Related structure data
Related structure data | 44129MC 9b33C 9b34C 9b35C 9b37C 9b38C 9b39C C: citing same article (ref.) M: map data used to model this data |
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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
-Protein , 2 types, 8 molecules ABCDEFGH
#1: Protein | Mass: 102976.586 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grik2, Glur6 / Production host: Homo sapiens (human) / References: UniProt: P42260 #2: Protein | Mass: 25622.385 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Canavalia ensiformis (jack bean) / References: UniProt: C0HJY1 |
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-Sugars , 7 types, 28 molecules
#3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: 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 #5: Polysaccharide | beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose- ...beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]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 #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 | Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Polysaccharide | Source method: isolated from a genetically manipulated source |
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-Non-polymers , 6 types, 38 molecules
#10: Chemical | ChemComp-2J9 / #11: Chemical | ChemComp-GLU / #12: Chemical | ChemComp-POV / ( #13: Chemical | ChemComp-CLR / #14: Chemical | ChemComp-ZN / #15: Chemical | ChemComp-CA / |
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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 |
-Sample preparation
Component | Name: full-length rat GluK2 tetramer in complex with two concanavalin A dimers Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES | ||||||||||||||||||||||||||||||||||||||||
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Molecular weight | Value: 0.51 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||||||||||||
Source (natural) | Organism: Rattus norvegicus (Norway rat) | ||||||||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Human embryonic kidney 293 / Plasmid: pEG BacMam | ||||||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 2.5 sec. / Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 5 / Num. of real images: 22990 |
Image scans | Width: 5760 / Height: 4092 |
-Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 8660229 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 109827 Details: This is composite map. Reference map: 4.29 A ATD: 3.5 A LBD-TMD: 3.4 A ConA: 3.58 A Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||
Refine LS restraints |
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