[English] 日本語
Yorodumi- PDB-8jpf: Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes -
+Open data
-Basic information
Entry | Database: PDB / ID: 8jpf | ||||||
---|---|---|---|---|---|---|---|
Title | Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes | ||||||
Components |
| ||||||
Keywords | SIGNALING PROTEIN / Biased signaling | ||||||
Function / homology | Function and homology information G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / positive regulation of inhibitory postsynaptic potential / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / L-glutamate import across plasma membrane / positive regulation of arachidonic acid secretion / regulation of respiratory gaseous exchange / negative regulation of release of sequestered calcium ion into cytosol ...G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / positive regulation of inhibitory postsynaptic potential / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / L-glutamate import across plasma membrane / positive regulation of arachidonic acid secretion / regulation of respiratory gaseous exchange / 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 / regulation of membrane depolarization / 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 / perikaryon / chemical synaptic transmission / G alpha (q) signalling events / dendritic spine / positive regulation of apoptotic process / membrane raft / G protein-coupled receptor signaling pathway / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.02 Å | ||||||
Authors | Duan, J. / Liu, H. / Zhao, F. / Yuan, Q. / Ji, Y. / Xu, H.E. | ||||||
Funding support | China, 1items
| ||||||
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
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8jpf.cif.gz | 67.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8jpf.ent.gz | 45.5 KB | Display | PDB format |
PDBx/mmJSON format | 8jpf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jp/8jpf ftp://data.pdbj.org/pub/pdb/validation_reports/jp/8jpf | HTTPS FTP |
---|
-Related structure data
Related structure data | 36478MC 8jpbC 8jpcC 8jpdC 8jpeC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein/peptide | Mass: 819.007 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
---|---|
#2: Protein | Mass: 46307.594 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NTSR1, NTRR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P30989 |
#3: Chemical | ChemComp-SRW / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Focused refiment structure of NTSR1 in NTSR1-GRK2-Galpha(q) complexes Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: DARK FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
3D reconstruction | Resolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 474232 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|