+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30566 | |||||||||
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Title | Human SECR in complex with an engineered Gs heterotrimer | |||||||||
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Sample |
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Function / homology | Function and homology information secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling ...secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling / embryonic digestive tract development / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G protein-coupled peptide receptor activity / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / diet induced thermogenesis / cytoplasmic microtubule / peptide hormone binding / photoreceptor outer segment / cardiac muscle cell apoptotic process / photoreceptor inner segment / response to nutrient levels / G protein-coupled receptor binding / hippocampus development / adenylate cyclase-activating G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / brain development / hormone activity / regulation of synaptic plasticity / Glucagon-type ligand receptors / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia / cell body / G alpha (s) signalling events / cell population proliferation / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / signaling receptor binding / GTPase activity / dendrite / protein-containing complex binding / extracellular space / extracellular region / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) / unidentified (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Fukuhara S / Kobayashi K / Kusakizako T / Shihoya W / Nureki O | |||||||||
Citation | Journal: Biochem Biophys Res Commun / Year: 2020 Title: Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein. Authors: Satoshi Fukuhara / Kazuhiro Kobayashi / Tsukasa Kusakizako / Wataru Iida / Masahiko Kato / Wataru Shihoya / Osamu Nureki / Abstract: Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is ...Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is involved in various processes, such as regulation of the pH of the duodenal content, food intake, and water homeostasis. Here, we report a cryo-electron microscopy structure of human SECR bound to secretin and an engineered Gs heterotrimer. The structure revealed the basic architecture of SECR and the secretin binding mode. A structural comparison of the SECR and PAC1R transmembrane domains revealed that transmembrane helices 1 and 2 play a prominent role in secretin recognition. Moreover, the extracellular domain of SECR is perpendicular to the TMD, unlike that of PAC1R. This comparison revealed the diverged peptide recognition mechanisms of these receptors, which belong to the same subgroup. Our structural information will facilitate drug discovery research for clinical applications. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_30566.map.gz | 3.7 MB | EMDB map data format | |
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Header (meta data) | emd-30566-v30.xml emd-30566.xml | 22.5 KB 22.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_30566_fsc.xml | 7.5 KB | Display | FSC data file |
Images | emd_30566.png | 71.6 KB | ||
Others | emd_30566_half_map_1.map.gz emd_30566_half_map_2.map.gz | 33.1 MB 33.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30566 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30566 | HTTPS FTP |
-Validation report
Summary document | emd_30566_validation.pdf.gz | 616.4 KB | Display | EMDB validaton report |
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Full document | emd_30566_full_validation.pdf.gz | 616 KB | Display | |
Data in XML | emd_30566_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | emd_30566_validation.cif.gz | 18.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30566 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30566 | HTTPS FTP |
-Related structure data
Related structure data | 7d3sMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_30566.map.gz / Format: CCP4 / Size: 35.3 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: 1.10667 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #2
File | emd_30566_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_30566_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : SECR-Gs complex
+Supramolecule #1: SECR-Gs complex
+Supramolecule #2: Secretin
+Supramolecule #3: Secretin receptor
+Supramolecule #4: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Supramolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #7: nanobody Nb35
+Macromolecule #1: Secretin
+Macromolecule #2: Secretin receptor
+Macromolecule #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: nanobody Nb35
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5.4 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 2142 / Average electron dose: 50.8 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |