+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35815 | |||||||||
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Title | ETB-Gi complex bound to Endotheline-1, focused on receptor | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Class A GPCR / Endothelin / Gi / Vasoactive peptide / PEPTIDE BINDING PROTEIN | |||||||||
Function / homology | Function and homology information 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 ...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 / body fluid secretion / 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 / histamine secretion / rough endoplasmic reticulum lumen / positive regulation of chemokine-mediated signaling pathway / positive regulation of odontogenesis / maternal process involved in parturition / regulation of glucose transmembrane transport / pharyngeal arch artery morphogenesis / endothelin receptor signaling pathway involved in heart process / semaphorin-plexin signaling pathway involved in axon guidance / epithelial fluid transport / podocyte differentiation / cardiac neural crest cell migration involved in outflow tract morphogenesis / negative regulation of hormone secretion / response to leptin / endothelin receptor signaling pathway / response to ozone / Weibel-Palade body / renal sodium ion absorption / positive regulation of cell growth involved in cardiac muscle cell development / artery smooth muscle contraction / glomerular filtration / axonogenesis involved in innervation / positive regulation of cation channel activity / positive regulation of prostaglandin secretion / cellular response to follicle-stimulating hormone stimulus / cellular response to luteinizing hormone stimulus / regulation of pH / negative regulation of nitric-oxide synthase biosynthetic process / cellular response to mineralocorticoid stimulus / positive regulation of urine volume / negative regulation of blood coagulation / respiratory gaseous exchange by respiratory system / basal part of cell / positive regulation of smooth muscle contraction / 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 / superoxide anion generation / axon extension / dorsal/ventral pattern formation / negative regulation of protein metabolic process / positive regulation of neutrophil chemotaxis / middle ear morphogenesis / positive regulation of signaling receptor activity / cellular response to glucocorticoid stimulus / cartilage development / prostaglandin biosynthetic process / nitric oxide transport / cellular response to fatty acid / positive regulation of heart rate / cellular response to organic substance / branching involved in blood vessel morphogenesis / response to testosterone / response to dexamethasone / positive regulation of cardiac muscle hypertrophy / negative regulation of smooth muscle cell apoptotic process / membrane depolarization / thyroid gland development / regulation of vasoconstriction / positive regulation of cell size / canonical Wnt signaling pathway / response to amino acid / cellular response to interleukin-1 / positive regulation of calcium-mediated signaling / protein kinase A signaling / positive regulation of JUN kinase activity / transport vesicle / ERK1 and ERK2 cascade / positive regulation of vascular associated smooth muscle cell proliferation / response to amphetamine / cellular response to transforming growth factor beta stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to muscle stretch / cellular response to calcium ion / mitochondrion organization / Peptide ligand-binding receptors / positive regulation of mitotic nuclear division / positive regulation of endothelial cell migration / response to activity Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.13 Å | |||||||||
Authors | Sano FK / Akasaka H / Shihoya W / Nureki O | |||||||||
Funding support | Japan, 1 items
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Citation | Journal: Elife / Year: 2023 Title: Cryo-EM structure of the endothelin-1-ET-G complex. Authors: Fumiya K Sano / Hiroaki Akasaka / Wataru Shihoya / Osamu Nureki / Abstract: The endothelin ET receptor is a promiscuous G-protein coupled receptor that is activated by vasoactive peptide endothelins. ET signaling induces reactive astrocytes in the brain and vasorelaxation in ...The endothelin ET receptor is a promiscuous G-protein coupled receptor that is activated by vasoactive peptide endothelins. ET signaling induces reactive astrocytes in the brain and vasorelaxation in vascular smooth muscle. Consequently, ET agonists are expected to be drugs for neuroprotection and improved anti-tumor drug delivery. Here, we report the cryo-electron microscopy structure of the endothelin-1-ET-G complex at 2.8 Å resolution, with complex assembly stabilized by a newly established method. Comparisons with the inactive ET receptor structures revealed how endothelin-1 activates the ET receptor. The NPxxY motif, essential for G-protein activation, is not conserved in ET, resulting in a unique structural change upon G-protein activation. Compared with other GPCR-G-protein complexes, ET binds G in the shallowest position, further expanding the diversity of G-protein binding modes. This structural information will facilitate the elucidation of G-protein activation and the rational design of ET agonists. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35815.map.gz | 1.6 MB | EMDB map data format | |
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Header (meta data) | emd-35815-v30.xml emd-35815.xml | 14.7 KB 14.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_35815_fsc.xml | 6.6 KB | Display | FSC data file |
Images | emd_35815.png | 41.4 KB | ||
Masks | emd_35815_msk_1.map | 1.8 MB | Mask map | |
Filedesc metadata | emd-35815.cif.gz | 5.7 KB | ||
Others | emd_35815_half_map_1.map.gz emd_35815_half_map_2.map.gz | 1.6 MB 1.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35815 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35815 | HTTPS FTP |
-Related structure data
Related structure data | 8iy6MC 8iy5C 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_35815.map.gz / Format: CCP4 / Size: 1.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.162 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_35815_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35815_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35815_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of Endothelin-1, ETB, and Gi
Entire | Name: Complex of Endothelin-1, ETB, and Gi |
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Components |
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-Supramolecule #1: Complex of Endothelin-1, ETB, and Gi
Supramolecule | Name: Complex of Endothelin-1, ETB, and Gi / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Endothelin type B receptor
Macromolecule | Name: Endothelin type B receptor / 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: 67.492219 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: EERGFPPDRA TPLLQTAEIM TPPTKTLWPK GDYKDDDDKL APAEVPKGDR TAGSPPRTIS PPPCQGPIEI KETFKYINTV VSCLVFVLG IIGNSTLLRI IYKNKCMRNG PNILIASLAL GDLLHIVIDI PINVYKLLAE DWPFGAEMCK LVPFIQKASV G ITVLSLCA ...String: EERGFPPDRA TPLLQTAEIM TPPTKTLWPK GDYKDDDDKL APAEVPKGDR TAGSPPRTIS PPPCQGPIEI KETFKYINTV VSCLVFVLG IIGNSTLLRI IYKNKCMRNG PNILIASLAL GDLLHIVIDI PINVYKLLAE DWPFGAEMCK LVPFIQKASV G ITVLSLCA LSIDRYRAVA SWSRIKGIGV PKWTAVEIVL IWVVSVVLAV PEAIGFDIIT MDYKGSYLRI CLLHPVQKTA FM QFYKTAK DWWLFSFYFC LPLAITAFFY TLMTCEMLRK KSGMQIALND HLKQRREVAK TVFCLVLVFA LCWLPLHLSR ILK LTLYNQ NDPNRCELLS FLLVLDYIGI NMASLNSCIN PIALYLVSKR FKNCFKSCLC CWCQSFEEKQ SLEEKQSCLK FKAN DHGYD NFRSSNKYSS SGSGGGGSGG SSSGGVFTLE DFVGDWEQTA AYNLDQVLEQ GGVSSLLQNL AVSVTPIQRI VRSGE NALK IDIHVIIPYE GLSADQMAQI EEVFKVVYPV DDHHFKVILP YGTLVIDGVT PNMLNYFGRP YEGIAVFDGK KITVTG TLW NGNKIIDERL ITPDGSMLFR VTINSGGSGG GGSGGSSSGG LEVLFQ |
-Macromolecule #2: Endothelin-1
Macromolecule | Name: Endothelin-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: 2.497951 KDa |
Sequence | String: CSCSSLMDKE CVYFCHLDII W UniProtKB: Endothelin-1 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 8 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 10408 / Average exposure time: 2.3 sec. / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |