+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34663 | |||||||||
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Title | Cryo-EM structure of endothelin1-bound ETAR-Gq complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | ET1 / ETAR / Gq / scFv16 / MEMBRANE PROTEIN | |||||||||
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 | |||||||||
Biological species | Homo (humans) / Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.01 Å | |||||||||
Authors | Yuan Q / Jiang Y / Xu HE / Ji Y / Duan J | |||||||||
Funding support | China, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_34663.map.gz | 56.6 MB | EMDB map data format | |
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Header (meta data) | emd-34663-v30.xml emd-34663.xml | 20 KB 20 KB | Display Display | EMDB header |
Images | emd_34663.png | 37.6 KB | ||
Filedesc metadata | emd-34663.cif.gz | 6.6 KB | ||
Others | emd_34663_half_map_1.map.gz emd_34663_half_map_2.map.gz | 49.6 MB 49.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34663 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34663 | HTTPS FTP |
-Validation report
Summary document | emd_34663_validation.pdf.gz | 800.6 KB | Display | EMDB validaton report |
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Full document | emd_34663_full_validation.pdf.gz | 800.2 KB | Display | |
Data in XML | emd_34663_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | emd_34663_validation.cif.gz | 14.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34663 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34663 | HTTPS FTP |
-Related structure data
Related structure data | 8hcqMC 8hbdC 8hcxC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_34663.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_34663_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_34663_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : ET1-ETAR-Gq-scFv16 complex
Entire | Name: ET1-ETAR-Gq-scFv16 complex |
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Components |
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-Supramolecule #1: ET1-ETAR-Gq-scFv16 complex
Supramolecule | Name: ET1-ETAR-Gq-scFv16 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #6, #5, #1-#4 |
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Source (natural) | Organism: Homo (humans) |
-Macromolecule #1: Guanine nucleotide-binding protein G(q) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(q) subunit alpha-1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 28.084832 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...String: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRKEFV DISTASGDGR HICYPHFTCA VDTENARRIF NDCKDIILQM NL REYNLV |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 41.055867 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWNGSSGG GGSGGGGSSG VSGWRLFKKI S UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 30.363043 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS ...String: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS GGGGSADIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLEL |
-Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #5: Endothelin-1
Macromolecule | Name: Endothelin-1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 2.497951 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: CSCSSLMDKE CVYFCHLDII W UniProtKB: Endothelin-1 |
-Macromolecule #6: Endothelin-1 receptor,Oplophorus-luciferin 2-monooxygenase cataly...
Macromolecule | Name: Endothelin-1 receptor,Oplophorus-luciferin 2-monooxygenase catalytic subunit chimera type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO / EC number: Oplophorus-luciferin 2-monooxygenase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 69.969906 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASDN PERYSTNLS NHVDDFTTFR GTELSFLVTT HQPTNLVLPS NGSMHNYCPQ QTKITSAFKY INTVISCTIF IVGMVGNATL L RIIYQNKC ...String: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASDN PERYSTNLS NHVDDFTTFR GTELSFLVTT HQPTNLVLPS NGSMHNYCPQ QTKITSAFKY INTVISCTIF IVGMVGNATL L RIIYQNKC MRNGPNALIA SLALGDLIYV VIDLPINVFK LLAGRWPFDH NDFGVFLCKL FPFLQKSSVG ITVLNLCALS VD RYRAVAS WSRVQGIGIP LVTAIEIVSI WILSFILAIP EAIGFVMVPF EYRGEQHKTC MLNATSKFME FYQDVKDWWL FGF YFCMPL VCTAIFYTLM TCEMLNRRNG SLRIALSEHL KQRREVAKTV FCLVVIFALC WFPLHLSRIL KKTVYNEMDK NRCE LLSFL LLMDYIGINL ATMNSCINPI ALYFVSKKFK NCFQSCLCCC CYQSKSLMTS VPMNGTSIQV FTLEDFVGDW EQTAA YNLD QVLEQGGVSS LLQNLAVSVT PIQRIVRSGE NALKIDIHVI IPYEGLSADQ MAQIEEVFKV VYPVDDHHFK VILPYG TLV IDGVTPNMLN YFGRPYEGIA VFDGKKITVT GTLWNGNKII DERLITPDGS MLFRVTINS UniProtKB: Endothelin-1 receptor, Oplophorus-luciferin 2-monooxygenase catalytic subunit |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 510197 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |