[English] 日本語
Yorodumi
- PDB-8jpc: cryo-EM structure of NTSR1-GRK2-Galpha(q) complexes 2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8jpc
Titlecryo-EM structure of NTSR1-GRK2-Galpha(q) complexes 2
Components
  • Beta-adrenergic receptor kinase 1
  • Guanine nucleotide-binding protein G(q) subunit alpha
  • NTS(8-13)
  • Neurotensin receptor type 1
KeywordsSIGNALING PROTEIN / Biased signaling
Function / homology
Function and homology information


Calmodulin induced events / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic-receptor kinase / Activation of SMO / G protein-coupled neurotensin receptor activity / Edg-2 lysophosphatidic acid receptor binding / inositol phosphate catabolic process / alpha-2A adrenergic receptor binding / symmetric synapse ...Calmodulin induced events / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic-receptor kinase / Activation of SMO / G protein-coupled neurotensin receptor activity / Edg-2 lysophosphatidic acid receptor binding / inositol phosphate catabolic process / alpha-2A adrenergic receptor binding / symmetric synapse / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / tachykinin receptor signaling pathway / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / negative regulation of striated muscle contraction / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / positive regulation of protein localization to cilium / Cargo recognition for clathrin-mediated endocytosis / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / desensitization of G protein-coupled receptor signaling pathway / regulation of membrane depolarization / cytoplasmic side of mitochondrial outer membrane / regulation of platelet activation / entrainment of circadian clock / positive regulation of arachidonate secretion / L-glutamate import across plasma membrane / regulation of the force of heart contraction / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential / positive regulation of smoothened signaling pathway / negative regulation of systemic arterial blood pressure / G protein-coupled receptor internalization / negative regulation of release of sequestered calcium ion into cytosol / positive regulation of glutamate secretion / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / G alpha (s) signalling events / G alpha (q) signalling events / temperature homeostasis / response to lipid / positive regulation of inositol phosphate biosynthetic process / detection of temperature stimulus involved in sensory perception of pain / phototransduction, visible light / photoreceptor outer segment / regulation of signal transduction / neuropeptide signaling pathway / postsynaptic cytosol / cardiac muscle contraction / adenylate cyclase-activating adrenergic receptor signaling pathway / enzyme regulator activity / response to prostaglandin E / GTPase activator activity / viral genome replication / Peptide ligand-binding receptors / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / positive regulation of release of sequestered calcium ion into cytosol / dendritic shaft / adult locomotory behavior / learning / cell projection / intracellular protein transport / G protein-coupled receptor binding / G protein-coupled receptor activity / cytoplasmic side of plasma membrane / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / terminal bouton / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / blood coagulation / ADP signalling through P2Y purinoceptor 1 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / heterotrimeric G-protein complex / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / heart development / G protein activity / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / nuclear membrane / perikaryon / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / dendritic spine / chemical synaptic transmission / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / protein phosphorylation / protein kinase activity / postsynapse / protein stabilization / positive regulation of apoptotic process / G protein-coupled receptor signaling pathway / membrane raft / lysosomal membrane / GTPase activity / positive regulation of gene expression
Similarity search - Function
Neurotensin receptor / Neurotensin type 1 receptor / G-protein alpha subunit, group Q / GPCR kinase / Regulator of G-protein Signalling 4, domain 2 / Regulator of G-protein Signalling 4; domain 2 / Regulator of G protein signaling domain / RGS domain / RGS domain profile. / Regulator of G protein signalling domain ...Neurotensin receptor / Neurotensin type 1 receptor / G-protein alpha subunit, group Q / GPCR kinase / Regulator of G-protein Signalling 4, domain 2 / Regulator of G-protein Signalling 4; domain 2 / Regulator of G protein signaling domain / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS, subdomain 2 / RGS domain superfamily / Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB) / PH-domain like / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / PH-like domain superfamily / Roll / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase / Orthogonal Bundle / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
TETRAFLUOROALUMINATE ION / GUANOSINE-5'-DIPHOSPHATE / Chem-SRW / STAUROSPORINE / Beta-adrenergic receptor kinase 1 / Neurotensin receptor type 1 / Guanine nucleotide-binding protein G(q) subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
Bos taurus (domestic cattle)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.07 Å
AuthorsDuan, J. / Liu, H. / Zhao, F. / Yuan, Q. / Ji, Y. / Xu, H.E.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: 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
DepositionJun 11, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 9, 2023Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Mask / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Mask / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Mask / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Mask / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Aug 9, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Aug 16, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation_author.identifier_ORCID
Revision 1.2Aug 30, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Nov 6, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification
Revision 1.4Jun 25, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
Revision 1.1Jun 25, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
L: NTS(8-13)
R: Neurotensin receptor type 1
G: Beta-adrenergic receptor kinase 1
Q: Guanine nucleotide-binding protein G(q) subunit alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)169,5429
Polymers168,0544
Non-polymers1,4885
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
Protein/peptide , 1 types, 1 molecules L

#1: Protein/peptide NTS(8-13)


Mass: 819.007 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

-
Protein , 3 types, 3 molecules RGQ

#2: Protein Neurotensin receptor type 1 / NT-R-1 / NTR1 / High-affinity levocabastine-insensitive neurotensin receptor / NTRH


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: Protein Beta-adrenergic receptor kinase 1 / Beta-ARK-1 / G-protein-coupled receptor kinase 2


Mass: 79644.727 Da / Num. of mol.: 1 / Mutation: A292P,R295I,S455D
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (domestic cattle) / Gene: GRK2, ADRBK1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P21146, beta-adrenergic-receptor kinase
#4: Protein Guanine nucleotide-binding protein G(q) subunit alpha / Guanine nucleotide-binding protein alpha-q


Mass: 41282.895 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAQ, GAQ / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P50148

-
Non-polymers , 5 types, 5 molecules

#5: Chemical ChemComp-SRW / 2-[{2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl}(methyl)amino]ethan-1-ol


Mass: 450.548 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H31FN4O2
#6: Chemical ChemComp-STU / STAUROSPORINE


Mass: 466.531 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H26N4O3 / Comment: antibiotic*YM
#7: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O11P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: GDP, energy-carrying molecule*YM
#8: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#9: Chemical ChemComp-ALF / TETRAFLUOROALUMINATE ION


Mass: 102.975 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: AlF4 / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: NTSR1-GRK2-Galpha(q) complexes 2 / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: DARK FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.07 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 233943 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00310837
ELECTRON MICROSCOPYf_angle_d0.67814666
ELECTRON MICROSCOPYf_dihedral_angle_d7.4861444
ELECTRON MICROSCOPYf_chiral_restr0.0441604
ELECTRON MICROSCOPYf_plane_restr0.0061851

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more