+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21972 | |||||||||||||||
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Title | Human secretin receptor Gs complex | |||||||||||||||
Map data | post-processed consensus refinement | |||||||||||||||
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-coupled peptide receptor activity / cytoplasmic microtubule / diet induced thermogenesis / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / response to nutrient levels / trans-Golgi network membrane / G protein-coupled receptor binding / hippocampus development / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / brain development / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of synaptic plasticity / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / hormone activity / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / platelet aggregation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / signaling receptor binding / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular space / extracellular exosome / extracellular region Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.3 Å | |||||||||||||||
Authors | Piper SJ / Belousoff MJ / Danev R | |||||||||||||||
Funding support | United States, Australia, United Kingdom, 4 items
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Citation | Journal: Nat Commun / Year: 2020 Title: Structure and dynamics of the active Gs-coupled human secretin receptor. Authors: Maoqing Dong / Giuseppe Deganutti / Sarah J Piper / Yi-Lynn Liang / Maryam Khoshouei / Matthew J Belousoff / Kaleeckal G Harikumar / Christopher A Reynolds / Alisa Glukhova / Sebastian G B ...Authors: Maoqing Dong / Giuseppe Deganutti / Sarah J Piper / Yi-Lynn Liang / Maryam Khoshouei / Matthew J Belousoff / Kaleeckal G Harikumar / Christopher A Reynolds / Alisa Glukhova / Sebastian G B Furness / Arthur Christopoulos / Radostin Danev / Denise Wootten / Patrick M Sexton / Laurence J Miller / Abstract: The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation ...The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD. | |||||||||||||||
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_21972.map.gz | 7.2 MB | EMDB map data format | |
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Header (meta data) | emd-21972-v30.xml emd-21972.xml | 29.5 KB 29.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_21972_fsc.xml | 10.2 KB | Display | FSC data file |
Images | emd_21972.png | 37.6 KB | ||
Masks | emd_21972_msk_1.map | 91.1 MB | Mask map | |
Others | emd_21972_additional_1.map.gz emd_21972_additional_2.map.gz emd_21972_additional_3.map.gz emd_21972_half_map_1.map.gz emd_21972_half_map_2.map.gz | 8.8 MB 57.3 MB 71.3 MB 71.4 MB 71.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21972 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21972 | HTTPS FTP |
-Validation report
Summary document | emd_21972_validation.pdf.gz | 598.6 KB | Display | EMDB validaton report |
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Full document | emd_21972_full_validation.pdf.gz | 598.1 KB | Display | |
Data in XML | emd_21972_validation.xml.gz | 17.4 KB | Display | |
Data in CIF | emd_21972_validation.cif.gz | 22.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21972 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21972 | HTTPS FTP |
-Related structure data
Related structure data | 6wzgMC 6wi9C 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_21972.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | post-processed consensus refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_21972_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: wider mask post-processed consensus refinement
File | emd_21972_additional_1.map | ||||||||||||
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Annotation | wider mask post-processed consensus refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Focussed receptor refinement, post-processed
File | emd_21972_additional_2.map | ||||||||||||
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Annotation | Focussed receptor refinement, post-processed | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: unsharpened map
File | emd_21972_additional_3.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Secretin receptor Gs complex half volume map 1
File | emd_21972_half_map_1.map | ||||||||||||
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Annotation | Secretin receptor Gs complex half volume map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Secretin receptor Gs complex half volume map 2
File | emd_21972_half_map_2.map | ||||||||||||
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Annotation | Secretin receptor Gs complex half volume map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Gs coupled secretin complex with secretin peptide
+Supramolecule #1: Gs coupled secretin complex with secretin peptide
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Supramolecule #3: Nanobody35
+Supramolecule #4: Secretin
+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: Nanobody35
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 8.1 mg/mL |
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Buffer | pH: 7.4 |
Grid | Material: GOLD |
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) / Detector mode: COUNTING / Average electron dose: 52.9 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |