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Yorodumi- EMDB-36478: Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36478 | |||||||||
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Title | Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Biased signaling / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / regulation of membrane depolarization / positive regulation of arachidonate secretion / L-glutamate import across plasma membrane / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential ...G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / regulation of membrane depolarization / positive regulation of arachidonate secretion / L-glutamate import across plasma membrane / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential / negative regulation of release of sequestered calcium ion into cytosol / negative regulation of systemic arterial blood pressure / positive regulation of glutamate secretion / positive regulation of inositol phosphate biosynthetic process / temperature homeostasis / response to lipid / detection of temperature stimulus involved in sensory perception of pain / neuropeptide signaling pathway / Peptide ligand-binding receptors / adult locomotory behavior / positive regulation of release of sequestered calcium ion into cytosol / dendritic shaft / learning / G protein-coupled receptor activity / terminal bouton / cytoplasmic side of plasma membrane / G alpha (q) signalling events / chemical synaptic transmission / perikaryon / dendritic spine / positive regulation of apoptotic process / G protein-coupled receptor signaling pathway / membrane raft / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.02 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_36478.map.gz | 118 MB | EMDB map data format | |
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Header (meta data) | emd-36478-v30.xml emd-36478.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
Images | emd_36478.png | 26.1 KB | ||
Masks | emd_36478_msk_1.map | 125 MB | Mask map | |
Others | emd_36478_half_map_1.map.gz emd_36478_half_map_2.map.gz | 116 MB 116 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36478 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36478 | HTTPS FTP |
-Validation report
Summary document | emd_36478_validation.pdf.gz | 828.8 KB | Display | EMDB validaton report |
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Full document | emd_36478_full_validation.pdf.gz | 828.3 KB | Display | |
Data in XML | emd_36478_validation.xml.gz | 13.5 KB | Display | |
Data in CIF | emd_36478_validation.cif.gz | 15.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36478 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36478 | HTTPS FTP |
-Related structure data
Related structure data | 8jpfMC 8jpbC 8jpcC 8jpdC 8jpeC 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_36478.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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_36478_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36478_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36478_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes
Entire | Name: Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes |
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Components |
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-Supramolecule #1: Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes
Supramolecule | Name: Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: NTS
Macromolecule | Name: NTS / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 819.007 Da |
Sequence | String: RRPYIL |
-Macromolecule #2: Neurotensin receptor type 1
Macromolecule | Name: Neurotensin receptor type 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 46.307594 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MRLNSSAPGT PGTPAADPFQ RAQAGLEEAL LAPGFGNASG NASERVLAAP SSELDVNTDI YSKVLVTAVY LALFVVGTVG NTVTAFTLA RKKSLQSLQS TVHYHLGSLA LSDLLTLLLA MPVELYNFIW VHHPWAFGDA GCRGYYFLRD ACTYATALNV A SLSVERYL ...String: MRLNSSAPGT PGTPAADPFQ RAQAGLEEAL LAPGFGNASG NASERVLAAP SSELDVNTDI YSKVLVTAVY LALFVVGTVG NTVTAFTLA RKKSLQSLQS TVHYHLGSLA LSDLLTLLLA MPVELYNFIW VHHPWAFGDA GCRGYYFLRD ACTYATALNV A SLSVERYL AICHPFKAKT LMSRSRTKKF ISAIWLASAL LAVPMLFTMG EQNRSADGQH AGGLVCTPTI HTATVKVVIQ VN TFMSFIF PMVVISVLNT IIANKLTVMV RQAAEQGQVC TVGGEHSTFS MAIEPGRVQA LRHGVRVLRA VVIAFVVCWL PYH VRRLMF CYISDEQWTP FLYDFYHYFY MVTNALFYVS STINPILYNL VSANFRHIFL ATLACLCPVW RRRRKRPAFS RKAD SVSSN HTLSSNATRE TLY UniProtKB: Neurotensin receptor type 1 |
-Macromolecule #3: 2-[{2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]...
Macromolecule | Name: 2-[{2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl}(methyl)amino]ethan-1-ol type: ligand / ID: 3 / Number of copies: 1 / Formula: SRW |
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Molecular weight | Theoretical: 450.548 Da |
Chemical component information | ChemComp-SRW: |
-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: DARK FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 474232 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |