+Open data
-Basic information
Entry | Database: PDB / ID: 7xau | ||||||
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Title | Structure of somatostatin receptor 2 bound with octreotide. | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / G protein coupled receptor / Cryo-EM / SST analogues / Polypeptide drugs | ||||||
Function / homology | Function and homology information somatostatin receptor activity / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / peristalsis / Activation of the phototransduction cascade / neuropeptide binding / cellular response to glucocorticoid stimulus / Activation of G protein gated Potassium channels / G-protein activation ...somatostatin receptor activity / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / peristalsis / Activation of the phototransduction cascade / neuropeptide binding / cellular response to glucocorticoid stimulus / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / Adrenaline,noradrenaline inhibits insulin secretion / 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 / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / response to starvation / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / neuropeptide signaling pathway / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / forebrain development / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cerebellum development / Peptide ligand-binding receptors / Regulation of insulin secretion / G protein-coupled receptor binding / cellular response to estradiol stimulus / PDZ domain binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / response to peptide hormone / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / G alpha (s) signalling events / spermatogenesis / cell population proliferation / Extra-nuclear estrogen signaling / neuron projection / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / negative regulation of cell population proliferation / GTPase activity / centrosome / protein-containing complex binding / GTP binding / nucleolus / magnesium ion binding / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) synthetic construct (others) Bos taurus (cattle) Rattus (rat) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.97 Å | ||||||
Authors | Bo, Q. / Yang, F. / Li, Y.G. / Meng, X.Y. / Zhang, H.H. / Zhou, Y.X. / Ling, S.L. / Sun, D.M. / Lv, P. / Liu, L. ...Bo, Q. / Yang, F. / Li, Y.G. / Meng, X.Y. / Zhang, H.H. / Zhou, Y.X. / Ling, S.L. / Sun, D.M. / Lv, P. / Liu, L. / Shi, P. / Tian, C.L. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Discov / Year: 2022 Title: Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues. Authors: Qing Bo / Fan Yang / Yingge Li / Xianyu Meng / Huanhuan Zhang / Yingxin Zhou / Shenglong Ling / Demeng Sun / Pei Lv / Lei Liu / Pan Shi / Changlin Tian / Abstract: The endogenous cyclic tetradecapeptide SST14 was reported to stimulate all five somatostatin receptors (SSTR1-5) for hormone release, neurotransmission, cell growth arrest and cancer suppression. Two ...The endogenous cyclic tetradecapeptide SST14 was reported to stimulate all five somatostatin receptors (SSTR1-5) for hormone release, neurotransmission, cell growth arrest and cancer suppression. Two SST14-derived short cyclic SST analogues (lanreotide or octreotide) with improved stability and longer lifetime were developed as drugs to preferentially activate SSTR2 and treat acromegalia and neuroendocrine tumors. Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.85 Å, 2.97 Å, and 2.87 Å, respectively. Structural and functional analysis revealed that interactions between β-turn residues in SST analogues and transmembrane SSTR2 residues in the ligand-binding pocket are crucial for receptor binding and functional stimulation of the two SST14-derived cyclic octapeptides. Additionally, Q102, N276, and F294 could be responsible for the selectivity of lanreotide or octreotide for SSTR2 over SSTR1 or SSTR4. These results provide valuable insights into further rational development of SST analogue drugs targeting SSTR2. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xau.cif.gz | 218.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xau.ent.gz | 161.6 KB | Display | PDB format |
PDBx/mmJSON format | 7xau.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xa/7xau ftp://data.pdbj.org/pub/pdb/validation_reports/xa/7xau | HTTPS FTP |
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-Related structure data
Related structure data | 33099MC 7xatC 7xavC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules BCD
#2: Protein | Mass: 40472.082 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096 |
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#3: Protein | Mass: 38975.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62871 |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212 |
-Protein / Antibody / Protein/peptide , 3 types, 3 molecules AEF
#1: Protein | Mass: 63274.395 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) synthetic construct (others) Gene: SSTR2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P30874 |
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#5: Antibody | Mass: 32768.484 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus (rat) / Production host: Spodoptera frugiperda (fall armyworm) |
#6: Protein/peptide | Mass: 1022.263 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Details
Has ligand of interest | N |
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-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: The SST anologue octreotide bound somatostatin receptor 2 and Gi heterotrimer complex Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
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: SPOT SCAN |
Electron lens | Mode: DIFFRACTION / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.97 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 666575 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
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