[English] 日本語
Yorodumi
- PDB-8hcq: Cryo-EM structure of endothelin1-bound ETAR-Gq complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8hcq
TitleCryo-EM structure of endothelin1-bound ETAR-Gq complex
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Endothelin-1
  • Endothelin-1 receptor,Oplophorus-luciferin 2-monooxygenase catalytic subunit chimera
  • scFv16
KeywordsMEMBRANE PROTEIN / ET1 / ETAR / Gq / scFv16
Function / homology
Function and homology information


regulation of protein localization to cell leading edge / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / phospholipase D-activating G protein-coupled receptor signaling pathway / rhythmic excitation / endothelin receptor activity / peptide hormone secretion ...regulation of protein localization to cell leading edge / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / phospholipase D-activating G protein-coupled receptor signaling pathway / rhythmic excitation / endothelin receptor activity / peptide hormone secretion / endothelin B receptor binding / cellular response to human chorionic gonadotropin stimulus / positive regulation of artery morphogenesis / meiotic cell cycle process involved in oocyte maturation / semaphorin-plexin signaling pathway involved in axon guidance / body fluid secretion / neural crest cell fate commitment / atrial cardiac muscle tissue development / vein smooth muscle contraction / glomerular endothelium development / response to prostaglandin F / sympathetic neuron axon guidance / positive regulation of sarcomere organization / vascular associated smooth muscle cell development / noradrenergic neuron differentiation / positive regulation of renal sodium excretion / histamine secretion / leukocyte activation / maternal process involved in parturition / positive regulation of chemokine-mediated signaling pathway / cardiac chamber formation / rough endoplasmic reticulum lumen / heparin metabolic process / developmental pigmentation / pharyngeal arch artery morphogenesis / regulation of D-glucose transmembrane transport / positive regulation of odontogenesis / epithelial fluid transport / response to leptin / endothelin receptor signaling pathway involved in heart process / negative regulation of hormone secretion / cardiac neural crest cell migration involved in outflow tract morphogenesis / Weibel-Palade body / endothelin receptor signaling pathway / response to acetylcholine / sodium ion homeostasis / response to ozone / podocyte differentiation / positive regulation of cell growth involved in cardiac muscle cell development / podocyte apoptotic process / renal sodium ion absorption / embryonic skeletal system development / left ventricular cardiac muscle tissue morphogenesis / artery smooth muscle contraction / mesenchymal cell apoptotic process / glomerular filtration / protein transmembrane transport / enteric nervous system development / axonogenesis involved in innervation / positive regulation of cation channel activity / cranial skeletal system development / cellular response to follicle-stimulating hormone stimulus / cellular response to luteinizing hormone stimulus / : / negative regulation of nitric-oxide synthase biosynthetic process / positive regulation of prostaglandin secretion / renal albumin absorption / positive regulation of smooth muscle contraction / basal part of cell / respiratory gaseous exchange by respiratory system / cellular response to mineralocorticoid stimulus / regulation of pH / sympathetic nervous system development / response to salt / positive regulation of urine volume / phosphatidylinositol phospholipase C activity / positive regulation of hormone secretion / norepinephrine metabolic process / regulation of systemic arterial blood pressure by endothelin / vasoconstriction / : / negative regulation of blood coagulation / embryonic heart tube development / dorsal/ventral pattern formation / axon extension / superoxide anion generation / establishment of endothelial barrier / cellular response to glucocorticoid stimulus / aorta development / positive regulation of neutrophil chemotaxis / positive regulation of signaling receptor activity / cartilage development / middle ear morphogenesis / negative regulation of protein metabolic process / prostaglandin biosynthetic process / cellular response to fatty acid / neuromuscular process / nitric oxide transport / positive regulation of heart rate / neuron remodeling
Similarity search - Function
Endothelin receptor A / Endothelin receptor family / Endothelin-like toxin / Endothelin-like toxin, conserved site / Endothelin / : / Endothelin family / Endothelin family signature. / Endothelin / Calycin ...Endothelin receptor A / Endothelin receptor family / Endothelin-like toxin / Endothelin-like toxin, conserved site / Endothelin / : / Endothelin family / Endothelin family signature. / Endothelin / Calycin / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain superfamily / GGL domain / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta 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) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Endothelin-1 / Endothelin-1 receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Oplophorus-luciferin 2-monooxygenase catalytic subunit
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.01 Å
AuthorsYuan, Q. / Jiang, Y. / Xu, H.E. / Ji, Y. / Duan, J.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2023
Title: Structural basis of peptide recognition and activation of endothelin receptors.
Authors: Yujie Ji / Jia Duan / Qingning Yuan / Xinheng He / Gong Yang / Shengnan Zhu / Kai Wu / Wen Hu / Tianyu Gao / Xi Cheng / Hualiang Jiang / H Eric Xu / Yi Jiang /
Abstract: Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETR) and B ...Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETR) and B (ETR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETR and ETR bound to ET-1 and ETR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes.
History
DepositionNov 2, 2022Deposition site: PDBJ / Processing site: RCSB
Revision 1.0Mar 22, 2023Provider: repository / Type: Initial release
Revision 1.1Oct 4, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(q) subunit alpha-1
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
E: scFv16
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
L: Endothelin-1
R: Endothelin-1 receptor,Oplophorus-luciferin 2-monooxygenase catalytic subunit chimera


Theoretical massNumber of molelcules
Total (without water)179,8336
Polymers179,8336
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG

#1: Protein Guanine nucleotide-binding protein G(q) subunit alpha-1


Mass: 28084.832 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 41055.867 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7861.143 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768

-
Antibody / Protein/peptide / Protein , 3 types, 3 molecules ELR

#3: Antibody scFv16


Mass: 30363.043 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm)
#5: Protein/peptide Endothelin-1 / Preproendothelin-1 / PPET1


Mass: 2497.951 Da / Num. of mol.: 1 / Fragment: UNP residues 53-73
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EDN1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P05305
#6: Protein Endothelin-1 receptor,Oplophorus-luciferin 2-monooxygenase catalytic subunit chimera / Endothelin receptor type A / ET-A / ETA-R / hET-AR / 19kOLase


Mass: 69969.906 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EDNRA, ETA, ETRA / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P25101, UniProt: Q9GV45, Oplophorus-luciferin 2-monooxygenase

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: ET1-ETAR-Gq-scFv16 complex / Type: COMPLEX / Entity ID: #6, #5, #1-#4 / Source: MULTIPLE SOURCES
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Homo (humans)9605
31Mus musculus (house mouse)10090
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: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.20.1_4487: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 510197 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0039308
ELECTRON MICROSCOPYf_angle_d0.58112596
ELECTRON MICROSCOPYf_dihedral_angle_d3.7991250
ELECTRON MICROSCOPYf_chiral_restr0.0391416
ELECTRON MICROSCOPYf_plane_restr0.0051598

+
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