+Open data
-Basic information
Entry | Database: PDB / ID: 8hcq | ||||||
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Title | Cryo-EM structure of endothelin1-bound ETAR-Gq complex | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / ET1 / ETAR / Gq / scFv16 | ||||||
Function / homology | Function and homology information regulation of protein localization to cell leading edge / : / endothelin receptor activity / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / meiotic cell cycle process involved in oocyte maturation / phospholipase D-activating G protein-coupled receptor signaling pathway / endothelin B receptor binding ...regulation of protein localization to cell leading edge / : / endothelin receptor activity / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / meiotic cell cycle process involved in oocyte maturation / phospholipase D-activating G protein-coupled receptor signaling pathway / endothelin B receptor binding / rhythmic excitation / peptide hormone secretion / neural crest cell fate commitment / sympathetic neuron axon guidance / Oplophorus-luciferin 2-monooxygenase / body fluid secretion / Oplophorus-luciferin 2-monooxygenase activity / glomerular endothelium development / vein smooth muscle contraction / noradrenergic neuron differentiation / response to prostaglandin F / positive regulation of renal sodium excretion / leukocyte activation / positive regulation of sarcomere organization / vascular associated smooth muscle cell development / atrial cardiac muscle tissue development / histamine secretion / heparin metabolic process / rough endoplasmic reticulum lumen / positive regulation of chemokine-mediated signaling pathway / maternal process involved in parturition / cardiac chamber formation / pharyngeal arch artery morphogenesis / regulation of glucose transmembrane transport / positive regulation of odontogenesis / endothelin receptor signaling pathway involved in heart process / protein transmembrane transport / epithelial fluid transport / cardiac neural crest cell migration involved in outflow tract morphogenesis / negative regulation of hormone secretion / response to leptin / endothelin receptor signaling pathway / podocyte differentiation / response to ozone / Weibel-Palade body / sodium ion homeostasis / developmental pigmentation / response to acetylcholine / renal sodium ion absorption / mesenchymal cell apoptotic process / glomerular filtration / positive regulation of cell growth involved in cardiac muscle cell development / artery smooth muscle contraction / podocyte apoptotic process / left ventricular cardiac muscle tissue morphogenesis / embryonic skeletal system development / axonogenesis involved in innervation / enteric nervous system development / positive regulation of cation channel activity / cellular response to follicle-stimulating hormone stimulus / positive regulation of prostaglandin secretion / cellular response to luteinizing hormone stimulus / cranial skeletal system development / renal albumin absorption / negative regulation of nitric-oxide synthase biosynthetic process / cellular response to mineralocorticoid stimulus / positive regulation of urine volume / regulation of pH / respiratory gaseous exchange by respiratory system / basal part of cell / positive regulation of smooth muscle contraction / sympathetic nervous system development / semaphorin-plexin signaling pathway involved in axon guidance / phosphatidylinositol phospholipase C activity / norepinephrine metabolic process / positive regulation of hormone secretion / regulation of systemic arterial blood pressure by endothelin / vasoconstriction / protein kinase C-activating G protein-coupled receptor signaling pathway / embryonic heart tube development / negative regulation of blood coagulation / superoxide anion generation / dorsal/ventral pattern formation / establishment of endothelial barrier / axon extension / positive regulation of neutrophil chemotaxis / middle ear morphogenesis / positive regulation of signaling receptor activity / cellular response to glucocorticoid stimulus / cartilage development / aorta development / prostaglandin biosynthetic process / neuromuscular process / negative regulation of protein metabolic process / nitric oxide transport / cellular response to fatty acid / neuron remodeling / : / branching involved in blood vessel morphogenesis / positive regulation of heart rate Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.01 Å | ||||||
Authors | Yuan, Q. / Jiang, Y. / Xu, H.E. / Ji, Y. / Duan, J. | ||||||
Funding support | China, 1items
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Citation | Journal: 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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8hcq.cif.gz | 247.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8hcq.ent.gz | 187.6 KB | Display | PDB format |
PDBx/mmJSON format | 8hcq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hc/8hcq ftp://data.pdbj.org/pub/pdb/validation_reports/hc/8hcq | HTTPS FTP |
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-Related structure data
Related structure data | 34663MC 8hbdC 8hcxC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | 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) |
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#2: Protein | 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 | 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 | 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) |
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#5: Protein/peptide | 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 | 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
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: ET1-ETAR-Gq-scFv16 complex / Type: COMPLEX / Entity ID: #6, #5, #1-#4 / Source: MULTIPLE SOURCES | ||||||||||||
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Source (natural) |
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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 |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 510197 / Symmetry type: POINT | ||||||||||||||||||||||||
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