+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23014 | |||||||||
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Title | GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) | |||||||||
Map data | GluK2/K5 with CNQX (full-length map) | |||||||||
Sample |
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Function / homology | Function and homology information regulation of synaptic vesicle fusion to presynaptic active zone membrane / protein retention in ER lumen / chemical synaptic transmission, postsynaptic / 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 / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity ...regulation of synaptic vesicle fusion to presynaptic active zone membrane / protein retention in ER lumen / chemical synaptic transmission, postsynaptic / 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 / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity / regulation of JNK cascade / ubiquitin conjugating enzyme binding / receptor clustering / modulation of excitatory postsynaptic potential / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / neuronal action potential / behavioral fear response / regulation of postsynaptic membrane potential / positive regulation of synaptic transmission / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / monoatomic ion transmembrane transport / 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 / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic transmission, glutamatergic / establishment of localization in cell / PDZ domain binding / cellular response to glucose stimulus / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / modulation of chemical synaptic transmission / terminal bouton / SH3 domain binding / intracellular calcium ion homeostasis / positive regulation of neuron apoptotic process / serine-type endopeptidase inhibitor activity / presynaptic membrane / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynaptic density / axon / neuronal cell body / ubiquitin protein ligase binding / glutamatergic synapse / synapse / dendrite / endoplasmic reticulum / extracellular space / identical protein binding / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) / Aequorea victoria (jellyfish) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.3 Å | |||||||||
Authors | Khanra N / Brown PMGE / Perozzo AM / Bowie D / Meyerson JR | |||||||||
Citation | Journal: Elife / Year: 2021 Title: Architecture and structural dynamics of the heteromeric GluK2/K5 kainate receptor. Authors: Nandish Khanra / Patricia Mge Brown / Amanda M Perozzo / Derek Bowie / Joel R Meyerson / Abstract: Kainate receptors (KARs) are L-glutamate-gated ion channels that regulate synaptic transmission and modulate neuronal circuits. KARs have strict assembly rules and primarily function as heteromeric ...Kainate receptors (KARs) are L-glutamate-gated ion channels that regulate synaptic transmission and modulate neuronal circuits. KARs have strict assembly rules and primarily function as heteromeric receptors in the brain. A longstanding question is how KAR heteromer subunits organize and coordinate together to fulfill their signature physiological roles. Here we report structures of the GluK2/GluK5 heteromer in apo, antagonist-bound, and desensitized states. The receptor assembles with two copies of each subunit, ligand binding domains arranged as two heterodimers and GluK5 subunits proximal to the channel. Strikingly, during desensitization, GluK2, but not GluK5, subunits undergo major structural rearrangements to facilitate channel closure. We show how the large conformational differences between antagonist-bound and desensitized states are mediated by the linkers connecting the pore helices to the ligand binding domains. This work presents the first KAR heteromer structure, reveals how its subunits are organized, and resolves how the heteromer can accommodate functionally distinct closed channel structures. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23014.map.gz | 117.9 MB | EMDB map data format | |
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Header (meta data) | emd-23014-v30.xml emd-23014.xml | 17.5 KB 17.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23014_fsc.xml emd_23014_fsc_2.xml | 11.5 KB 11.2 KB | Display Display | FSC data file |
Images | emd_23014.png | 57.4 KB | ||
Others | emd_23014_additional_1.map.gz emd_23014_additional_2.map.gz | 98.6 MB 96.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23014 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23014 | HTTPS FTP |
-Related structure data
Related structure data | 7ks0MC 7ks3C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | |
EM raw data | EMPIAR-10659 (Title: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) Data size: 5.9 TB Data #1: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) [micrographs - multiframe] Data #2: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) [micrographs - multiframe] Data #3: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) [micrographs - multiframe] Data #4: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) [picked particles - single frame - processed] Data #5: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) [picked particles - single frame - processed]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23014.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | GluK2/K5 with CNQX (full-length map) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.096 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: GluK2/K5 with CNQX (ATD map)
File | emd_23014_additional_1.map | ||||||||||||
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Annotation | GluK2/K5 with CNQX (ATD map) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: GluK2/K5 with CNQX (LBD-TMD map)
File | emd_23014_additional_2.map | ||||||||||||
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Annotation | GluK2/K5 with CNQX (LBD-TMD map) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)
Entire | Name: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) |
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Components |
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-Supramolecule #1: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)
Supramolecule | Name: GluK2/K5 with 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293S GnTI- |
-Macromolecule #1: Glutamate receptor ionotropic, kainate 5,Green fluorescent protei...
Macromolecule | Name: Glutamate receptor ionotropic, kainate 5,Green fluorescent protein chimera type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Aequorea victoria (jellyfish) |
Molecular weight | Theoretical: 123.676812 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MPAELLLLLI VAFANPSCQV LSSLRMAAIL DDQTVCGRGE RLALALAREQ INGIIEVPAK ARVEVDIFEL QRDSQYETTD TMCQILPKG VVSVLGPSSS PASASTVSHI CGEKEIPHIK VGPEETPRLQ YLRFASVSLY PSNEDVSLAV SRILKSFNYP S ASLICAKA ...String: MPAELLLLLI VAFANPSCQV LSSLRMAAIL DDQTVCGRGE RLALALAREQ INGIIEVPAK ARVEVDIFEL QRDSQYETTD TMCQILPKG VVSVLGPSSS PASASTVSHI CGEKEIPHIK VGPEETPRLQ YLRFASVSLY PSNEDVSLAV SRILKSFNYP S ASLICAKA ECLLRLEELV RGFLISKETL SVRMLDDSRD PTPLLKEIRD DKVSTIIIDA NASISHLVLR KASELGMTSA FY KYILTTM DFPILHLDGI VEDSSNILGF SMFNTSHPFY PEFVRSLNMS WRENCEASTY PGPALSAALM FDAVHVVVSA VRE LNRSQE IGVKPLACTS ANIWPHGTSL MNYLRMVEYD GLTGRVEFNS KGQRTNYTLR ILEKSRQGHR EIGVWYSNRT LAMN ATTLD INLSQTLANK TLVVTTILEN PYVMRRPNFQ ALSGNERFEG FCVDMLRELA ELLRFRYRLR LVEDGLYGAP EPNGS WTGM VGELINRKAD LAVAAFTITA EREKVIDFSK PFMTLGISIL YRVHMGRKPG YFSFLDPFSP AVWLFMLLAY LAVSVV LFL AARLSPYEWY NPHPSLRARP HILENQYTLG NSLWFPVGGF MQQGSEIMPR ALSTRIVSGV WWAFTLIIIS SYTANLA AF LTVQRMEVPV ESADDLADQT NIEYGTIHAG STMTFFQNSR YQTYQRMWNY MQSKQPSVFV KSTEEGIARV LNSRYAFL L ESTMNEYHRR LNCNLTQIGG LLDTKGYGIG MPLGSPFRDE ITLAILQLQE NNRLEILKRK WWEGGRCPKE EDHRAKGLG MENIGGIFVV LIAGLIIAVF VAVMEFIYKS RAEAKRMKGL VPRGSAAAAM VSKGEELFTG VVPILVELDG DVNGHKFSVS GEGEGDATY GKLTLKFICT TGKLPVPWPT LVTTLTYGVQ CFSRYPDHMK QHDFFKSAMP EGYVQERTIF FKDDGNYKTR A EVKFEGDT LVNRIELKGI DFKEDGNILG HKLEYNYNSH NVYIMADKQK NGIKVNFKIR HNIEDGSVQL ADHYQQNTPI GD GPVLLPD NHYLSTQSKL SKDPNEKRDH MVLLEFVTAA GITLGMDELY KSGLRTETSQ VAPA |
-Macromolecule #2: Glutamate receptor ionotropic, kainate 2
Macromolecule | Name: Glutamate receptor ionotropic, kainate 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 105.981617 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSF EASKKACDQL SLGVAAIFGP SHSSSANAVQ SICNALGVPH IQTRWKHQVS DNKDSFYVSL YPDFSSLSRA I LDLVQFFK ...String: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSF EASKKACDQL SLGVAAIFGP SHSSSANAVQ SICNALGVPH IQTRWKHQVS DNKDSFYVSL YPDFSSLSRA I LDLVQFFK WKTVTVVYDD STGLIRLQEL IKAPSRYNLR LKIRQLPADT KDAKPLLKEM KRGKEFHVIF DCSHEMAAGI LK QALAMGM MTEYYHYIFT TLDLFALDVE PYRYSGVNMT GFRILNTENT QVSSIIEKWS MERLQAPPKP DSGLLDGFMT TDA ALMYDA VHVVSVAVQQ FPQMTVSSLQ CNRHKPWRFG TRFMSLIKEA HWEGLTGRIT FNKTNGLRTD FDLDVISLKE EGLE KIGTW DPASGLNMTE SQKGKPANIT DSLSNRSLIV TTILEEPYVL FKKSDKPLYG NDRFEGYCID LLRELSTILG FTYEI RLVE DGKYGAQDDV NGQWNGMVRE LIDHKADLAV APLAITYVRE KVIDFSKPFM TLGISILYRK PNGTNPGVFS FLNPLS PDI WMYVLLAYLG VSVVLFVIAR FSPYEWYNPH PSNPDSDVVE NNFTLLNSFW FGVGALMQQG SELMPKALST RIVGGIW WF FTLIIISSYT ANLAAFLTVE RMESPIDSAD DLAKQTKIEY GAVEDGATMT FFKKSKISTY DKMWAFMSSR RQSVLVKS N EEGIQRVLTS DYAFLMESTT IEFVTQRNCN LTQIGGLIDS KGYGVGTPMG SPYRDKITIA ILQLQEEGKL HMMKEKWWR GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG EFLYKSKKNA QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEE VINMHTFNDR RLPGKETMAS GLRSAWSHPQ FEKGGGSGGG SGGGSWSHPQ FEK |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3.7 mg/mL | |||||||||
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Buffer | pH: 8 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Details: Functionalized with PEG-thiol | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV | |||||||||
Details | 1 mM 6-Cyano-7-nitroquinoxaline-2,3-dione |
-Electron microscopy
Microscope | FEI TECNAI ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 51.5 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |