+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41092 | |||||||||
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Title | Quis-bound intermediate mGlu5 | |||||||||
Map data | Quis bound intermediate mGlu5 | |||||||||
Sample |
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Keywords | GPCR / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information A2A adenosine receptor binding / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / desensitization of G protein-coupled receptor signaling pathway / protein tyrosine kinase activator activity / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / G protein-coupled glutamate receptor signaling pathway ...A2A adenosine receptor binding / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / desensitization of G protein-coupled receptor signaling pathway / protein tyrosine kinase activator activity / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / : / glutamate receptor activity / Neurexins and neuroligins / regulation of synaptic transmission, glutamatergic / positive regulation of calcium-mediated signaling / protein tyrosine kinase binding / learning / dendritic shaft / locomotory behavior / G protein-coupled receptor activity / synapse organization / postsynaptic density membrane / Schaffer collateral - CA1 synapse / cognition / cellular response to amyloid-beta / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of MAPK cascade / learning or memory / dendritic spine / glutamatergic synapse / dendrite / regulation of DNA-templated transcription / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Krishna Kumar K / Wang H / Kobilka BK | |||||||||
Funding support | United States, 1 items
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Citation | Journal: bioRxiv / Year: 2023 Title: Step-wise activation of a Family C GPCR. Authors: Kaavya Krishna Kumar / Haoqing Wang / Chris Habrian / Naomi R Latorraca / Jun Xu / Evan S O'Brien / Chensong Zhang / Elizabeth Montabana / Antoine Koehl / Susan Marqusee / Ehud Y Isacoff / Brian K Kobilka / Abstract: Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine- ...Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine-rich domain (CRDs) to their 7-transmembrane (TM) domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the ECD to the G protein-coupling TM. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging we reveal distinct receptor conformations upon allosteric modulator and G protein binding. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41092.map.gz | 141 MB | EMDB map data format | |
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Header (meta data) | emd-41092-v30.xml emd-41092.xml | 13.6 KB 13.6 KB | Display Display | EMDB header |
Images | emd_41092.png | 54.1 KB | ||
Filedesc metadata | emd-41092.cif.gz | 6.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41092 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41092 | HTTPS FTP |
-Validation report
Summary document | emd_41092_validation.pdf.gz | 458.2 KB | Display | EMDB validaton report |
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Full document | emd_41092_full_validation.pdf.gz | 457.8 KB | Display | |
Data in XML | emd_41092_validation.xml.gz | 6.6 KB | Display | |
Data in CIF | emd_41092_validation.cif.gz | 7.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41092 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41092 | HTTPS FTP |
-Related structure data
Related structure data | 8t7hMC 8t6jC 8t8mC 8taoC 41807 41808 M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_41092.map.gz / Format: CCP4 / Size: 149.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Quis bound intermediate mGlu5 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.111 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Metabotropic glutamate receptor 5 in complex with Quis
Entire | Name: Metabotropic glutamate receptor 5 in complex with Quis |
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Components |
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-Supramolecule #1: Metabotropic glutamate receptor 5 in complex with Quis
Supramolecule | Name: Metabotropic glutamate receptor 5 in complex with Quis type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Metabotropic glutamate receptor 5
Macromolecule | Name: Metabotropic glutamate receptor 5 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 98.868297 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDAAQSSER RVVAHMPGDI IIGALFSVHH QPTVDKVHER KCGAVREQYG IQRVEAMLHT LERINSDPT LLPNITLGCE IRDSCWHSAV ALEQSIEFIR DSLISSEEEE GLVRCVDGSS SSFRSKKPIV GVIGPGSSSV A IQVQNLLQ ...String: MKTIIALSYI FCLVFADYKD DDDAAQSSER RVVAHMPGDI IIGALFSVHH QPTVDKVHER KCGAVREQYG IQRVEAMLHT LERINSDPT LLPNITLGCE IRDSCWHSAV ALEQSIEFIR DSLISSEEEE GLVRCVDGSS SSFRSKKPIV GVIGPGSSSV A IQVQNLLQ LFNIPQIAYS ATSMDLSDKT LFKYFMRVVP SDAQQARAMV DIVKRYNWTY VSAVHTEGNY GESGMEAFKD MS AKEGICI AHSYKIYSNA GEQSFDKLLK KLTSHLPKAR VVACFCEGMT VRGLLMAMRR LGLAGEFLLL GSDGWADRYD VTD GYQREA VGGITIKLQS PDVKWFDDYY LKLRPETNHR NPWFQEFWQH RFQCRLEGFP QENSKYNKTC NSSLTLKTHH VQDS KMGFV INAIYSMAYG LHNMQMSLCP GYAGLCDAMK PIDGRKLLES LMKTNFTGVS GDTILFDENG DSPGRYEIMN FKEMG KDYF DYINVGSWDN GELKMDDDEV WSKKSNIIRS VCSEPCEKGQ IKVIRKGEVS CCWTCTPCKE NEYVFDEYTC KACQLG SWP TDDLTGCDLI PVQYLRWGDP EPIAAVVFAC LGLLATLFVT VVFIIYRDTP VVKSSSRELC YIILAGICLG YLCTFCL IA KPKQIYCYLQ RIGIGLSPAM SYSALVTKTN RIARILAGSK KKICTKKPRF MSACAQLVIA FILICIQLGI IVALFIME P PDIMHDYPSI REVYLICNTT NLGVVTPLGY NGLLILSCTF YAFKTRNVPA NFNEAKYIAF TMYTTCIIWL AFVPIYFGS NYKIITMCFS VSLSATVALG CMFVPKVYII LAKPERNVRS AFTTSTVVRM HVGDGKSSSA ASRSSSLVNL WKRRGSSGET L UniProtKB: Metabotropic glutamate receptor 5 |
-Macromolecule #2: Nanobody 43
Macromolecule | Name: Nanobody 43 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 13.354672 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: QVQLVESGGG LVQAGGSLRL SCAASGRTFT SYAMGWFRQA PGKERESVAA ISSSGGSTHY ADSVKGRFTI SRDNSKNTVY LQMNSLKPE DTAVYYCAAA MYGSRWPDWE YDYWGQGTQV TVSS |
-Macromolecule #3: (S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID
Macromolecule | Name: (S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID type: ligand / ID: 3 / Number of copies: 2 / Formula: QUS |
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Molecular weight | Theoretical: 189.126 Da |
Chemical component information | ChemComp-QUS: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 211019 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |