+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34667 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of Endothelin1-bound ETBR-Gq complex | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | ET1 / ETAR / Gq / scFv16 / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information enteric smooth muscle cell differentiation / response to endothelin / endothelin receptor activity / negative regulation of neuron maturation / aldosterone metabolic process / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / chordate pharynx development ...enteric smooth muscle cell differentiation / response to endothelin / endothelin receptor activity / negative regulation of neuron maturation / aldosterone metabolic process / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / chordate pharynx development / meiotic cell cycle process involved in oocyte maturation / phospholipase D-activating G protein-coupled receptor signaling pathway / rhythmic excitation / endothelin B receptor binding / peptide hormone secretion / neural crest cell fate commitment / sympathetic neuron axon guidance / positive regulation of artery morphogenesis / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / glomerular endothelium development / vein smooth muscle contraction / body fluid secretion / regulation of fever generation / noradrenergic neuron differentiation / response to prostaglandin F / positive regulation of sarcomere organization / leukocyte activation / positive regulation of renal sodium excretion / histamine secretion / heparin metabolic process / positive regulation of chemokine-mediated signaling pathway / maternal process involved in parturition / positive regulation of penile erection / neuroblast migration / rough endoplasmic reticulum lumen / pharyngeal arch artery morphogenesis / regulation of glucose transmembrane transport / posterior midgut development / positive regulation of odontogenesis / endothelin receptor signaling pathway involved in heart process / 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 / Weibel-Palade body / developmental pigmentation / podocyte differentiation / response to ozone / renal sodium ion absorption / protein transmembrane transport / glomerular filtration / positive regulation of cell growth involved in cardiac muscle cell development / artery smooth muscle contraction / response to sodium phosphate / enteric nervous system development / axonogenesis involved in innervation / positive regulation of cation channel activity / renal sodium excretion / renin secretion into blood stream / cellular response to follicle-stimulating hormone stimulus / positive regulation of prostaglandin secretion / cellular response to luteinizing hormone stimulus / melanocyte differentiation / renal albumin absorption / negative regulation of nitric-oxide synthase biosynthetic process / cellular response to mineralocorticoid stimulus / basal part of cell / respiratory gaseous exchange by respiratory system / positive regulation of urine volume / positive regulation of smooth muscle contraction / response to salt / regulation of pH / semaphorin-plexin signaling pathway involved in axon guidance / negative regulation of adenylate cyclase activity / peripheral nervous system development / positive regulation of hormone secretion / regulation of systemic arterial blood pressure by endothelin / vasoconstriction / : / regulation of epithelial cell proliferation / embryonic heart tube development / negative regulation of blood coagulation / type 1 angiotensin receptor binding / dorsal/ventral pattern formation / establishment of endothelial barrier / axon extension / superoxide anion generation / positive regulation of neutrophil chemotaxis / positive regulation of signaling receptor activity / cartilage development / middle ear morphogenesis / cellular response to glucocorticoid stimulus / neural crest cell migration / prostaglandin biosynthetic process / negative regulation of protein metabolic process / nitric oxide transport / cellular response to fatty acid / branching involved in blood vessel morphogenesis Similarity search - Function | |||||||||
Biological species | Homo (humans) / Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Yuan Q / Jiang Y / Xu HE / Ji Y / Duan J | |||||||||
Funding support | China, 1 items
| |||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_34667.map.gz | 57.1 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-34667-v30.xml emd-34667.xml | 19.9 KB 19.9 KB | Display Display | EMDB header |
Images | emd_34667.png | 42.3 KB | ||
Filedesc metadata | emd-34667.cif.gz | 6.6 KB | ||
Others | emd_34667_half_map_1.map.gz emd_34667_half_map_2.map.gz | 49.4 MB 49.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34667 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34667 | HTTPS FTP |
-Validation report
Summary document | emd_34667_validation.pdf.gz | 673.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_34667_full_validation.pdf.gz | 672.8 KB | Display | |
Data in XML | emd_34667_validation.xml.gz | 12 KB | Display | |
Data in CIF | emd_34667_validation.cif.gz | 14.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34667 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34667 | HTTPS FTP |
-Related structure data
Related structure data | 8hcxMC 8hbdC 8hcqC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_34667.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_34667_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_34667_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : ET1-ETAR-Gq-scFv16 complex
Entire | Name: ET1-ETAR-Gq-scFv16 complex |
---|---|
Components |
|
-Supramolecule #1: ET1-ETAR-Gq-scFv16 complex
Supramolecule | Name: ET1-ETAR-Gq-scFv16 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
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 |
---|---|
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 |
---|---|
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: Endothelin receptor type B,Oplophorus-luciferin 2-monooxygenase c...
Macromolecule | Name: Endothelin receptor type B,Oplophorus-luciferin 2-monooxygenase catalytic subunit chimera type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: Oplophorus-luciferin 2-monooxygenase |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 67.88232 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDH HHHHHHHEER GFPPDRATPL LQTAEIMTPP TKTLWPKGSN ASLARSLAP AEVPKGDRTA GSPPRTISPP PCQGPIEIKE TFKYINTVVS CLVFVLGIIG NSTLLRIIYK NKCMRNGPNI L IASLALGD ...String: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDH HHHHHHHEER GFPPDRATPL LQTAEIMTPP TKTLWPKGSN ASLARSLAP AEVPKGDRTA GSPPRTISPP PCQGPIEIKE TFKYINTVVS CLVFVLGIIG NSTLLRIIYK NKCMRNGPNI L IASLALGD LLHIVIDIPI NVYKLLAEDW PFGAEMCKLV PFIQKASVGI TVLSLCALSI DRYRAVASWS RIKGIGVPKW TA VEIVLIW VVSVVLAVPE AIGFDIITMD YKGSYLRICL LHPVQKTAFM QFYKTAKDWW LFSFYFCLPL AITAFFYTLM TCE MLRKKS GMQIALNDHL KQRREVAKTV FCLVLVFALC WLPLHLSRIL KLTLYNQNDP NRCELLSFLL VLDYIGINMA SLNS CINPI ALYLVSKRFK NCFKSCLCCW CQSFEEKQSL EEKQSCLKFK VFTLEDFVGD WEQTAAYNLD QVLEQGGVSS LLQNL AVSV TPIQRIVRSG ENALKIDIHV IIPYEGLSAD QMAQIEEVFK VVYPVDDHHF KVILPYGTLV IDGVTPNMLN YFGRPY EGI AVFDGKKITV TGTLWNGNKI IDERLITPDG SMLFRVTINS UniProtKB: Endothelin receptor type B, Oplophorus-luciferin 2-monooxygenase catalytic subunit |
-Macromolecule #4: Endothelin-1
Macromolecule | Name: Endothelin-1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
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 #5: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
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 #6: 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: 6 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
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 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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 |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 373655 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |