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Yorodumi- PDB-7t10: CryoEM structure of somatostatin receptor 2 in complex with somat... -
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-Basic information
Entry | Database: PDB / ID: 7t10 | ||||||
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Title | CryoEM structure of somatostatin receptor 2 in complex with somatostatin-14 and Gi3 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN/SIGNALING PROTEIN / GPCR / Receptor / Complex / MEMBRANE PROTEIN / MEMBRANE PROTEIN-SIGNALING PROTEIN complex | ||||||
Function / homology | Function and homology information somatostatin signaling pathway / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / somatostatin receptor activity / MECP2 regulates transcription of neuronal ligands / negative regulation of luteinizing hormone secretion / positive regulation of eating behavior / sensory perception of temperature stimulus / hormone-mediated apoptotic signaling pathway ...somatostatin signaling pathway / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / somatostatin receptor activity / MECP2 regulates transcription of neuronal ligands / negative regulation of luteinizing hormone secretion / positive regulation of eating behavior / sensory perception of temperature stimulus / hormone-mediated apoptotic signaling pathway / adenylate cyclase-inhibiting opioid receptor signaling pathway / G protein-coupled opioid receptor activity / conditioned place preference / G protein-coupled opioid receptor signaling pathway / peristalsis / positive regulation of dopamine secretion / positive regulation of potassium ion transmembrane transport / sensory perception / maternal behavior / negative regulation of adenylate cyclase activity / neuropeptide binding / receptor serine/threonine kinase binding / response to acidic pH / hyperosmotic response / GTP metabolic process / cellular response to glucocorticoid stimulus / response to steroid hormone / positive regulation of p38MAPK cascade / dopamine receptor signaling pathway / eating behavior / response to starvation / neuronal dense core vesicle / behavioral response to cocaine / regulation of postsynaptic membrane neurotransmitter receptor levels / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of macroautophagy / estrous cycle / Adenylate cyclase inhibitory pathway / GABA-ergic synapse / neuropeptide signaling pathway / response to amino acid / axon terminus / MECP2 regulates neuronal receptors and channels / forebrain development / regulation of cell migration / sensory perception of pain / digestion / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cerebellum development / Peptide ligand-binding receptors / response to nutrient / locomotory behavior / cellular response to estradiol stimulus / G protein-coupled receptor binding / PDZ domain binding / cellular response to glucose stimulus / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / response to insulin / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / hormone activity / synaptic vesicle membrane / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / response to estrogen / sensory perception of taste / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / signaling receptor complex adaptor activity Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||
Authors | Robertson, M.J. / Skinotis, G. | ||||||
Funding support | 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2022 Title: Plasticity in ligand recognition at somatostatin receptors. Authors: Michael J Robertson / Justin G Meyerowitz / Ouliana Panova / Kenneth Borrelli / Georgios Skiniotis / Abstract: Somatostatin is a signaling peptide that plays a pivotal role in physiologic processes relating to metabolism and growth through its actions at somatostatin receptors (SSTRs). Members of the SSTR ...Somatostatin is a signaling peptide that plays a pivotal role in physiologic processes relating to metabolism and growth through its actions at somatostatin receptors (SSTRs). Members of the SSTR subfamily, particularly SSTR2, are key drug targets for neuroendocrine neoplasms, with synthetic peptide agonists currently in clinical use. Here, we show the cryogenic-electron microscopy structures of active-state SSTR2 in complex with heterotrimeric G and either the endogenous ligand SST14 or the FDA-approved drug octreotide. Complemented by biochemical assays and molecular dynamics simulations, these structures reveal key details of ligand recognition and receptor activation at SSTRs. We find that SSTR ligand recognition is highly diverse, as demonstrated by ligand-induced conformational changes in ECL2 and substantial sequence divergence across subtypes in extracellular regions. Despite this complexity, we rationalize several known sources of SSTR subtype selectivity and identify an additional interaction for specific binding. These results provide valuable insights for structure-based drug discovery at SSTRs. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7t10.cif.gz | 206.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7t10.ent.gz | 161.1 KB | Display | PDB format |
PDBx/mmJSON format | 7t10.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t1/7t10 ftp://data.pdbj.org/pub/pdb/validation_reports/t1/7t10 | HTTPS FTP |
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-Related structure data
Related structure data | 25586MC 7t11C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10931 (Title: Cryogenic electron microscopy of somatostatin receptor 2/SST14/Gi3 complex Data size: 4.5 TB Data #1: Raw movies of SSTR2/SST14/Gi3 complex collected on a K3 [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#2: Protein | Mass: 40584.156 Da / Num. of mol.: 1 / Mutation: S47N, G203A, E245A, A326S Source method: isolated from a genetically manipulated source Details: dominant negative / Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI3 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P08754 |
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#3: Protein | Mass: 37671.102 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
-Protein / Protein/peptide / Antibody / Non-polymers , 4 types, 8 molecules RPS
#1: Protein | Mass: 45784.211 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Somatostatin receptor type 2 with intracellular loop 3 (ICL3) replaced with the ICL3 from the Kappa-type opioid receptor Source: (gene. exp.) Homo sapiens (human) / Gene: SSTR2, OPRK1, OPRK / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P30874, UniProt: P41145 |
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#5: Protein/peptide | Mass: 1641.909 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P61278 |
#6: Antibody | Mass: 27784.896 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm) |
#7: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Somatostatin receptor 2 in complex with Somatostatin-14 and Gi3. Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES |
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Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 1.04 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 442863 / Symmetry type: POINT |