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Yorodumi- PDB-7xmt: CryoEM structure of somatostatin receptor 4 (SSTR4) with Gi1 and ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7xmt | |||||||||||||||||||||||||||
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Title | CryoEM structure of somatostatin receptor 4 (SSTR4) with Gi1 and J-2156 | |||||||||||||||||||||||||||
Components |
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Keywords | STRUCTURAL PROTEIN / G protein-coupled receptor / somatostatin receptor 2 / cryo-EM | |||||||||||||||||||||||||||
Function / homology | Function and homology information somatostatin receptor activity / positive regulation of arachidonate secretion / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide binding / cellular response to glucocorticoid stimulus / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway ...somatostatin receptor activity / positive regulation of arachidonate secretion / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide binding / cellular response to glucocorticoid stimulus / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / forebrain development / regulation of mitotic spindle organization / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Peptide ligand-binding receptors / Regulation of insulin secretion / G protein-coupled receptor binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GDP binding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / cell migration / signaling receptor complex adaptor activity / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / cell cortex / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / midbody / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / neuron projection / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / lysosomal membrane / cell division / GTPase activity / centrosome / synapse / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||||||||||||||||||||
Authors | Wenli, Z. / Shuo, H. / Na, Q. / Wenbo, Z. / Mengjie, L. / Dehua, Y. / Ming-Wei, W. / Wu, B. / Zhao, Q. | |||||||||||||||||||||||||||
Funding support | China, 8items
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Citation | Journal: Cell Res / Year: 2022 Title: Structural insights into ligand recognition and selectivity of somatostatin receptors. Authors: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / ...Authors: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / Michelle Y Shen / Yaping Sun / Qing Zhang / Yingli Ma / Wenge Zhong / Dehua Yang / Ming-Wei Wang / Beili Wu / Qiang Zhao / Abstract: Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for ...Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of G-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of G-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs. | |||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xmt.cif.gz | 209.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xmt.ent.gz | 152.6 KB | Display | PDB format |
PDBx/mmJSON format | 7xmt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xmt_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7xmt_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7xmt_validation.xml.gz | 39.1 KB | Display | |
Data in CIF | 7xmt_validation.cif.gz | 57.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xm/7xmt ftp://data.pdbj.org/pub/pdb/validation_reports/xm/7xmt | HTTPS FTP |
-Related structure data
Related structure data | 33304MC 7xmrC 7xmsC 7xn9C 7xnaC 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 ACB
#2: Protein | Mass: 40447.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Insecta environmental sample (insect) / References: UniProt: P63096 |
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#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: Insecta environmental sample (insect) / References: UniProt: P59768 |
#5: Protein | Mass: 38744.371 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Insecta environmental sample (insect) / References: UniProt: P62873 |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RS
#1: Protein | Mass: 40667.375 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SSTR4 / Production host: Insecta environmental sample (insect) / References: UniProt: P31391 |
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#3: Antibody | Mass: 31549.107 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Insecta environmental sample (insect) |
#6: Chemical | ChemComp-I8B / ( |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-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: Complex structure of somatostatin receptor 4 (SSTR4) with Gi and J-2156 Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Insecta environmental sample (insect) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: NICKEL/TITANIUM |
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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2300 nm / Nominal defocus min: 1300 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 600908 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
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