[English] 日本語
Yorodumi- PDB-7wj5: Cryo-EM structure of human somatostatin receptor 2 complex with i... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7wj5 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand binding specificity | ||||||
Components |
| ||||||
Keywords | MEMBRANE PROTEIN/IMMUNE SYSTEM / GPCR / agonist / heterotrimeric G-protein / cAMP / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information somatostatin receptor activity / peristalsis / neuropeptide binding / cellular response to glucocorticoid stimulus / response to starvation / 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 / peristalsis / neuropeptide binding / cellular response to glucocorticoid stimulus / response to starvation / 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 / cerebellum development / cellular response to estradiol stimulus / Regulation of insulin secretion / G protein-coupled receptor binding / PDZ domain binding / electron transport chain / 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 / 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 / spermatogenesis / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / neuron projection / iron ion binding / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / lysosomal membrane / cell division / GTPase activity / centrosome / heme binding / synapse / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Escherichia coli (E. coli) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.72 Å | ||||||
Authors | Heo, Y.S. / Yoon, E.J. / Jeon, Y.E. / Yun, J.-H. / Ishimoto, N. / Woo, H. / Park, S.Y. / Song, J. / Lee, W.T. | ||||||
Funding support | Korea, Republic Of, 1items
| ||||||
Citation | Journal: Elife / Year: 2022 Title: Cryo-EM structure of the human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand-binding specificity. Authors: Yunseok Heo / Eojin Yoon / Ye-Eun Jeon / Ji-Hye Yun / Naito Ishimoto / Hyeonuk Woo / Sam-Yong Park / Ji-Joon Song / Weontae Lee / Abstract: Somatostatin is a peptide hormone that regulates endocrine systems by binding to G-protein-coupled somatostatin receptors. Somatostatin receptor 2 (SSTR2) is a human somatostatin receptor and is ...Somatostatin is a peptide hormone that regulates endocrine systems by binding to G-protein-coupled somatostatin receptors. Somatostatin receptor 2 (SSTR2) is a human somatostatin receptor and is highly implicated in hormone disorders, cancers, and neurological diseases. Here, we report the high-resolution cryo-EM structure of full-length human SSTR2 bound to the agonist somatostatin (SST-14) in complex with inhibitory G (G) proteins. Our structural and mutagenesis analyses show that seven transmembrane helices form a deep pocket for ligand binding and that SSTR2 recognizes the highly conserved Trp-Lys motif of SST-14 at the bottom of the pocket. Furthermore, our sequence analysis combined with AlphaFold modeled structures of other SSTR isoforms provide a structural basis for the mechanism by which SSTR family proteins specifically interact with their cognate ligands. This work provides the first glimpse into the molecular recognition mechanism of somatostatin receptors and a crucial resource to develop therapeutics targeting somatostatin receptors. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7wj5.cif.gz | 212.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7wj5.ent.gz | 162.9 KB | Display | PDB format |
PDBx/mmJSON format | 7wj5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7wj5_validation.pdf.gz | 864.9 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7wj5_full_validation.pdf.gz | 875.6 KB | Display | |
Data in XML | 7wj5_validation.xml.gz | 35.2 KB | Display | |
Data in CIF | 7wj5_validation.cif.gz | 53.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wj/7wj5 ftp://data.pdbj.org/pub/pdb/validation_reports/wj/7wj5 | HTTPS FTP |
-Related structure data
Related structure data | 32543MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 40415.031 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 |
---|---|
#2: Protein | Mass: 39418.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 |
#3: 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: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
-Antibody / Protein / Protein/peptide , 3 types, 3 molecules ERS
#4: Antibody | Mass: 28636.793 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm) |
---|---|
#5: Protein | Mass: 58163.469 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The fusion protein of expression tags, Soluble cytochrome b562, linker and Somatostatin receptor type 2. Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human) Gene: cybC, SSTR2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P0ABE7, UniProt: P30874 |
#6: Protein/peptide | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human SSTR2 and SST-14 complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | |||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Experimental value: NO | |||||||||||||||||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) / Cellular location: membrane / Tissue: Brain | |||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) / Strain: Sf9 / Plasmid: pFastBac | |||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||||||||||||||||||||||
Buffer component |
| |||||||||||||||||||||||||||||||||||
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: Quantifoil R2/1 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 75000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 55.04 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5523 |
Image scans | Movie frames/image: 50 / Used frames/image: 2-35 |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 6677042 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.72 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 320885 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||||||
Refine LS restraints |
|