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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31236 | |||||||||||||||
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Title | Cryo-EM structure of LY354740-bound mGlu2 homodimer | |||||||||||||||
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Function / homology | ![]() regulation of response to drug / group II metabotropic glutamate receptor activity / behavioral response to nicotine / intracellular glutamate homeostasis / astrocyte projection / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate secretion / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | ![]() ![]() | |||||||||||||||
![]() | Du J / Wang D / Fan H / Tai L / Lin S / Han S / Sun F / Wu B / Zhao Q | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of human mGlu2 and mGlu7 homo- and heterodimers. Authors: Juan Du / Dejian Wang / Hongcheng Fan / Chanjuan Xu / Linhua Tai / Shuling Lin / Shuo Han / Qiuxiang Tan / Xinwei Wang / Tuo Xu / Hui Zhang / Xiaojing Chu / Cuiying Yi / Peng Liu / Xiaomei ...Authors: Juan Du / Dejian Wang / Hongcheng Fan / Chanjuan Xu / Linhua Tai / Shuling Lin / Shuo Han / Qiuxiang Tan / Xinwei Wang / Tuo Xu / Hui Zhang / Xiaojing Chu / Cuiying Yi / Peng Liu / Xiaomei Wang / Yu Zhou / Jean-Philippe Pin / Philippe Rondard / Hong Liu / Jianfeng Liu / Fei Sun / Beili Wu / Qiang Zhao / ![]() ![]() Abstract: The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both ...The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties. Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation. | |||||||||||||||
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 | ![]() | 73 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.9 KB 12.9 KB | Display Display | ![]() |
Images | ![]() | 83.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7epbMC ![]() 7epaC ![]() 7epcC ![]() 7epdC ![]() 7epeC ![]() 7epfC 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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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 : LY354740-bound mGlu2 homodimer
Entire | Name: LY354740-bound mGlu2 homodimer |
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Components |
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-Supramolecule #1: LY354740-bound mGlu2 homodimer
Supramolecule | Name: LY354740-bound mGlu2 homodimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Metabotropic glutamate receptor 2
Macromolecule | Name: Metabotropic glutamate receptor 2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 94.061445 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DYKDDDDGAP EGPAKKVLTL EGDLVLGGLF PVHQKGGPAE DCGPVNEHRG IQRLEAMLFA LDRINRDPHL LPGVRLGAHI LDSCSKDTH ALEQALDFVR ASLSRGADGS RHICPDGSYA THGDAPTAIT GVIGGSYSDV SIQVANLLRL FQIPQISYAS T SAKLSDKS ...String: DYKDDDDGAP EGPAKKVLTL EGDLVLGGLF PVHQKGGPAE DCGPVNEHRG IQRLEAMLFA LDRINRDPHL LPGVRLGAHI LDSCSKDTH ALEQALDFVR ASLSRGADGS RHICPDGSYA THGDAPTAIT GVIGGSYSDV SIQVANLLRL FQIPQISYAS T SAKLSDKS RYDYFARTVP PDFFQAKAMA EILRFFNWTY VSTVASEGDY GETGIEAFEL EARARNICVA TSEKVGRAMS RA AFEGVVR ALLQKPSARV AVLFTRSEDA RELLAASQRL NASFTWVASD GWGALESVVA GSEGAAEGAI TIELASYPIS DFA SYFQSL DPWNNSRNPW FREFWEQRFR CSFRQRDCAA HSLRAVPFEQ ESKIMFVVNA VYAMAHALHN MHRALCPNTT RLCD AMRPV NGRRLYKDFV LNVKFDAPFR PADTHNEVRF DRFGDGIGRY NIFTYLRAGS GRYRYQKVGY WAEGLTLDTS LIPWA SPSA GPLPASRCSE PCLQNEVKSV QPGEVCCWLC IPCQPYEYRL DEFTCADCGL GYWPNASLTG CFELPQEYIR WGDAWA VGP VTIACLGALA TLFVLGVFVR HNATPVVKAA GRELCYILLG GVFLCYCMTF IFIAKPSTAV CTLRRLGLGT AFSVCYS AL LTKTNRIARI FGGAREGAQR PRFISPASQV AICLALISGQ LLIVVAWLVV EAPGTGKETA PERREVVTLR CNHRDASM L GSLAYNVLLI ALCTLYAFKT RKCPENFNEA KFIGFTMYTT CIIWLAFLPI FYVTSSDYRV QTTTMCVSVS LSGSVVLGC LFAPKLHIIL FQPQKNVEFL EVLFQGPGSG SWSHPQFEKG SGSWSHPQFE K |
-Macromolecule #2: Anti-RON nanobody
Macromolecule | Name: Anti-RON nanobody / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 15.207868 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: QVQLVQSGGG LVQAGGSLRL SCAASVRFFS INTMGWYRQA PGKQRELVAD ITSSGSTNYA DSGKGRFTIS RDNAKNTVYL QMNRLKPED TAVYYCHADY KYTTHNTAWG QGTQVTVSSG RPLEVLFQGP HHHHHHHH |
-Macromolecule #3: (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid
Macromolecule | Name: (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid type: ligand / ID: 3 / Number of copies: 2 / Formula: 40F |
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Molecular weight | Theoretical: 185.177 Da |
Chemical component information | ![]() ChemComp-40F: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 1.75 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 365101 |