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- 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 | ||||||
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![]() | MEMBRANE PROTEIN/SIGNALING PROTEIN / GPCR / Receptor / Complex / MEMBRANE PROTEIN / MEMBRANE PROTEIN-SIGNALING PROTEIN complex | ||||||
Function / homology | ![]() somatostatin signaling pathway / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / MECP2 regulates transcription of neuronal ligands / sensory perception of temperature stimulus / positive regulation of eating behavior / somatostatin receptor activity / adenylate cyclase-inhibiting opioid receptor signaling pathway / hormone-mediated apoptotic signaling pathway ...somatostatin signaling pathway / dynorphin receptor activity / response to acrylamide / regulation of saliva secretion / MECP2 regulates transcription of neuronal ligands / sensory perception of temperature stimulus / positive regulation of eating behavior / somatostatin receptor activity / adenylate cyclase-inhibiting opioid receptor signaling pathway / hormone-mediated apoptotic signaling pathway / G protein-coupled opioid receptor activity / negative regulation of luteinizing hormone secretion / G protein-coupled opioid receptor signaling pathway / peristalsis / positive regulation of dopamine secretion / sensory perception / positive regulation of potassium ion transmembrane transport / conditioned place preference / negative regulation of adenylate cyclase activity / maternal behavior / receptor serine/threonine kinase binding / neuropeptide binding / response to acidic pH / hyperosmotic response / GTP metabolic process / cellular response to glucocorticoid stimulus / response to steroid hormone / positive regulation of p38MAPK cascade / G protein-coupled dopamine receptor signaling pathway / eating behavior / neuronal dense core vesicle / regulation of postsynaptic membrane neurotransmitter receptor levels / response to starvation / behavioral response to cocaine / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of macroautophagy / estrous cycle / GABA-ergic synapse / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / response to amino acid / MECP2 regulates neuronal receptors and channels / axon terminus / forebrain development / regulation of cell migration / sensory perception of pain / digestion / T-tubule / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / cerebellum development / response to nutrient / sarcoplasmic reticulum / locomotory behavior / cellular response to estradiol stimulus / PDZ domain binding / G protein-coupled receptor binding / cellular response to glucose stimulus / response to nicotine / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / response to insulin / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / hormone activity / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / 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 / synaptic vesicle membrane / 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 / response to estrogen / 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 / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||
![]() | Robertson, M.J. / Skinotis, G. | ||||||
Funding support | 1items
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![]() | ![]() 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 |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 206.1 KB | Display | ![]() |
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PDB format | ![]() | 161.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 806.1 KB | Display | ![]() |
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Full document | ![]() | 810.7 KB | Display | |
Data in XML | ![]() | 33.8 KB | Display | |
Data in CIF | ![]() | 52.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 25586MC ![]() 7t11C M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 4.5 TB Data #1: Raw movies of SSTR2/SST14/Gi3 complex collected on a K3 [micrographs - multiframe]) |
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Links
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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.) ![]() ![]() |
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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.) ![]() ![]() |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein / Protein/peptide / Antibody / Non-polymers , 4 types, 8 molecules RPS![](data/chem/img/HOH.gif)
![](data/chem/img/HOH.gif)
#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.) ![]() ![]() ![]() |
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#5: Protein/peptide | Mass: 1641.909 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#6: Antibody | Mass: 27784.896 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#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 |
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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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.04 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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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 |