[English] 日本語
Yorodumi- EMDB-36476: Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36476 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | Biased signaling / SIGNALING PROTEIN | |||||||||
Function / homology | Function and homology information Calmodulin induced events / beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway ...Calmodulin induced events / beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway / negative regulation of striated muscle contraction / desensitization of G protein-coupled receptor signaling pathway / positive regulation of protein localization to cilium / Cargo recognition for clathrin-mediated endocytosis / regulation of the force of heart contraction / positive regulation of smoothened signaling pathway / G protein-coupled receptor internalization / G alpha (s) signalling events / G alpha (q) signalling events / regulation of signal transduction / cardiac muscle contraction / viral genome replication / cell projection / G protein-coupled receptor binding / intracellular protein transport / G protein-coupled acetylcholine receptor signaling pathway / presynapse / heart development / postsynapse / peptidyl-serine phosphorylation / protein kinase activity / symbiont entry into host cell / G protein-coupled receptor signaling pathway / protein phosphorylation / ATP binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Bos taurus (cattle) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.81 Å | |||||||||
Authors | Duan J / Liu H / Zhao F / Yuan Q / Ji Y / Xu HE | |||||||||
Funding support | China, 1 items
| |||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_36476.map.gz | 117.7 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-36476-v30.xml emd-36476.xml | 14.8 KB 14.8 KB | Display Display | EMDB header |
Images | emd_36476.png | 28.9 KB | ||
Masks | emd_36476_msk_1.map | 125 MB | Mask map | |
Others | emd_36476_half_map_1.map.gz emd_36476_half_map_2.map.gz | 116.1 MB 116.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36476 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36476 | HTTPS FTP |
-Related structure data
Related structure data | 8jpdMC 8jpbC 8jpcC 8jpeC 8jpfC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_36476.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_36476_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_36476_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_36476_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes
Entire | Name: Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes |
---|---|
Components |
|
-Supramolecule #1: Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes
Supramolecule | Name: Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Bos taurus (cattle) |
-Macromolecule #1: Beta-adrenergic receptor kinase 1
Macromolecule | Name: Beta-adrenergic receptor kinase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: beta-adrenergic-receptor kinase |
---|---|
Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 79.644727 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: ADLEAVLADV SYLMAMEKSK ATPAARASKK ILLPEPSIRS VMQKYLEDRG EVTFEKIFSQ KLGYLLFRDF CLKHLEEAKP LVEFYEEIK KYEKLETEEE RLVCSREIFD TYIMKELLAC SHPFSKSAIE HVQGHLVKKQ VPPDLFQPYI EEICQNLRGD V FQKFIESD ...String: ADLEAVLADV SYLMAMEKSK ATPAARASKK ILLPEPSIRS VMQKYLEDRG EVTFEKIFSQ KLGYLLFRDF CLKHLEEAKP LVEFYEEIK KYEKLETEEE RLVCSREIFD TYIMKELLAC SHPFSKSAIE HVQGHLVKKQ VPPDLFQPYI EEICQNLRGD V FQKFIESD KFTRFCQWKN VELNIHLTMN DFSVHRIIGR GGFGEVYGCR KADTGKMYAM KCLDKKRIKM KQGETLALNE RI MLSLVST GDCPFIVCMS YAFHTPDKLS FILDLMNGGD LHYHLSQHGV FSEPDMIFYA AEIILGLEHM HNRFVVYRDL KPA NILLDE HGHVRISDLG LACDFSKKKP HASVGTHGYM APEVLQKGVA YDSSADWFSL GCMLFKLLRG HSPFRQHKTK DKHE IDRMT LTMAVELPDS FSPELRSLLE GLLQRDVNRR LGCLGRGAQE VKESPFFRDL DWQMVFLQKY PPPLIPPRGE VNAAD AFDI GSFDEEDTKG IKLLDSDQEL YRNFPLTISE RWQQEVAETV FDTINAETDR LEARKKTKNK QLGHEEDYAL GKDCIM HGY MSKMGNPFLT QWQRRYFYLF PNRLEWRGEG EAPQSLLTME EIQSVEETQI KERKCLLLKI RGGKQFVLQC DSDPELV QW KKELRDAYRE AQQLVQRVPK MKNKPRSPVV ELSKVPLIQR GSANGL UniProtKB: Beta-adrenergic receptor kinase 1 |
-Macromolecule #2: STAUROSPORINE
Macromolecule | Name: STAUROSPORINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: STU |
---|---|
Molecular weight | Theoretical: 466.531 Da |
Chemical component information | ChemComp-STO: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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 |
---|---|
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.81 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 474232 |