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Yorodumi- EMDB-36477: Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q)... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36477 | |||||||||
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Title | Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q) complexes | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Biased signaling / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of platelet activation / phototransduction, visible light / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / action potential ...Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of platelet activation / phototransduction, visible light / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / action potential / activation of phospholipase C activity / photoreceptor outer segment / GTPase activator activity / G protein-coupled receptor binding / negative regulation of protein kinase activity / G-protein beta/gamma-subunit complex binding / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / heterotrimeric G-protein complex / blood coagulation / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (q) signalling events / nuclear membrane / protein stabilization / lysosomal membrane / GTPase activity / synapse / GTP binding / Golgi apparatus / extracellular exosome / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.91 Å | |||||||||
Authors | Duan J / Liu H / Zhao F / Yuan Q / Ji Y / Xu HE | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2023 Title: GPCR activation and GRK2 assembly by a biased intracellular agonist. Authors: Jia Duan / Heng Liu / Fenghui Zhao / Qingning Yuan / Yujie Ji / Xiaoqing Cai / Xinheng He / Xinzhu Li / Junrui Li / Kai Wu / Tianyu Gao / Shengnan Zhu / Shi Lin / Ming-Wei Wang / Xi Cheng / ...Authors: Jia Duan / Heng Liu / Fenghui Zhao / Qingning Yuan / Yujie Ji / Xiaoqing Cai / Xinheng He / Xinzhu Li / Junrui Li / Kai Wu / Tianyu Gao / Shengnan Zhu / Shi Lin / Ming-Wei Wang / Xi Cheng / Wanchao Yin / Yi Jiang / Dehua Yang / H Eric Xu / Abstract: Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands. The ...Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands. The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gα and the arrestin-biased ligand SBI-553. The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Gα protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36477.map.gz | 117.7 MB | EMDB map data format | |
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Header (meta data) | emd-36477-v30.xml emd-36477.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
Images | emd_36477.png | 18.4 KB | ||
Masks | emd_36477_msk_1.map | 125 MB | Mask map | |
Others | emd_36477_half_map_1.map.gz emd_36477_half_map_2.map.gz | 116 MB 116 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36477 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36477 | HTTPS FTP |
-Related structure data
Related structure data | 8jpeMC 8jpbC 8jpcC 8jpdC 8jpfC 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_36477.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_36477_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36477_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36477_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q)...
Entire | Name: Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q) complexes |
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Components |
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-Supramolecule #1: Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q)...
Supramolecule | Name: Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q) complexes type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Guanine nucleotide-binding protein G(q) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(q) subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 41.282895 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGERS RRELKLLLLG TGESGKSTFI KQMRIIHGSG YSDEDKRGFT KLVYQNIFTA MQAMIRAMD TLKIPYKYEH NKAHAQLVRE VDVEKVSAFE NPYVDAIKSL WNDPGIQECY DRRREYQLSD STKYYLNDLD R VADPAYLP ...String: MGCTLSAEDK AAVERSKMID RNLREDGERS RRELKLLLLG TGESGKSTFI KQMRIIHGSG YSDEDKRGFT KLVYQNIFTA MQAMIRAMD TLKIPYKYEH NKAHAQLVRE VDVEKVSAFE NPYVDAIKSL WNDPGIQECY DRRREYQLSD STKYYLNDLD R VADPAYLP TQQDVLRVRV PTTGIIEYPF DLQSVIFRMV DVGGQRSERR KWIHCFENVT SIMFLVALSE YDQVLVESDN EN RMEESKA LFRTIITYPW FQNSSVILFL NKKDLLEEKI MYSHLVDYFP EYDGPQRDAQ AAREFILKMF VDLNPDSDKI IYS HFTCAT DTENIRFVFA AVKDTILQLN LKEYNLV UniProtKB: Guanine nucleotide-binding protein G(q) subunit alpha |
-Macromolecule #2: GUANOSINE-5'-DIPHOSPHATE
Macromolecule | Name: GUANOSINE-5'-DIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 1 / Formula: GDP |
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Molecular weight | Theoretical: 443.201 Da |
Chemical component information | ChemComp-GDP: |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #4: TETRAFLUOROALUMINATE ION
Macromolecule | Name: TETRAFLUOROALUMINATE ION / type: ligand / ID: 4 / Number of copies: 1 / Formula: ALF |
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Molecular weight | Theoretical: 102.975 Da |
Chemical component information | ChemComp-ALF: |
-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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 474232 |