+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 / rhythmic excitation / endothelin B receptor binding / 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 / rhythmic excitation / endothelin B receptor binding / peptide hormone secretion / neural crest cell fate commitment / sympathetic neuron axon guidance / positive regulation of artery morphogenesis / glomerular endothelium development / vein smooth muscle contraction / body fluid secretion / noradrenergic neuron differentiation / response to prostaglandin F / positive regulation of sarcomere organization / leukocyte activation / positive regulation of renal sodium excretion / histamine secretion / positive regulation of chemokine-mediated signaling pathway / maternal process involved in parturition / rough endoplasmic reticulum lumen / pharyngeal arch artery morphogenesis / regulation of glucose transmembrane transport / 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 / podocyte differentiation / response to ozone / renal sodium ion absorption / glomerular filtration / positive regulation of cell growth involved in cardiac muscle cell development / artery smooth muscle contraction / axonogenesis involved in innervation / positive regulation of cation channel activity / cellular response to follicle-stimulating hormone stimulus / positive regulation of prostaglandin secretion / cellular response to luteinizing hormone stimulus / 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 / positive regulation of hormone secretion / regulation of systemic arterial blood pressure by endothelin / vasoconstriction / : / embryonic heart tube development / negative regulation of blood coagulation / dorsal/ventral pattern formation / 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 / prostaglandin biosynthetic process / negative regulation of protein metabolic process / nitric oxide transport / cellular response to fatty acid / branching involved in blood vessel morphogenesis / positive regulation of heart rate / : / response to testosterone / positive regulation of cardiac muscle hypertrophy / response to dexamethasone / negative regulation of smooth muscle cell apoptotic process / membrane depolarization / thyroid gland development / positive regulation of cell size / regulation of vasoconstriction / response to amino acid / canonical Wnt signaling pathway / cellular response to interleukin-1 / positive regulation of calcium-mediated signaling / positive regulation of JUN kinase activity / transport vesicle / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to transforming growth factor beta stimulus / protein kinase A signaling / response to amphetamine / cellular response to calcium ion / response to muscle stretch / ERK1 and ERK2 cascade / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of endothelial cell migration / positive regulation of mitotic nuclear division / mitochondrion organization 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 |
-Validation report
Summary document | emd_35815_validation.pdf.gz | 694.9 KB | Display | EMDB validaton report |
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Full document | emd_35815_full_validation.pdf.gz | 694.4 KB | Display | |
Data in XML | emd_35815_validation.xml.gz | 9.6 KB | Display | |
Data in CIF | emd_35815_validation.cif.gz | 12.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35815 ftp://ftp.pdbj.org/pub/emdb/validation_reports/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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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 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / 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 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |