+Open data
-Basic information
Entry | Database: PDB / ID: 8yw5 | ||||||||||||||||||||||||
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Title | Cryo-EM structure of the retatrutide-bound human GCGR-Gs complex | ||||||||||||||||||||||||
Components |
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Keywords | STRUCTURAL PROTEIN / G protein-coupled receptor / ligand recognition / receptor activation / unimolecular agonist / retatrutide | ||||||||||||||||||||||||
Function / homology | Function and homology information regulation of glycogen metabolic process / glucagon receptor activity / response to starvation / cellular response to glucagon stimulus / exocytosis / peptide hormone binding / hormone-mediated signaling pathway / cellular response to starvation / response to nutrient / guanyl-nucleotide exchange factor activity ...regulation of glycogen metabolic process / glucagon receptor activity / response to starvation / cellular response to glucagon stimulus / exocytosis / peptide hormone binding / hormone-mediated signaling pathway / cellular response to starvation / response to nutrient / guanyl-nucleotide exchange factor activity / generation of precursor metabolites and energy / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / regulation of blood pressure / 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 / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / 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 / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / glucose homeostasis / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / endosome / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / positive regulation of gene expression / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.84 Å | ||||||||||||||||||||||||
Authors | Li, W.Z. / Zhou, Q.T. / Cong, Z.T. / Yuan, Q.N. / Li, W.X. / Zhao, F.H. / Xu, H.E. / Zhao, L.H. / Yang, D.H. / Wang, M.W. | ||||||||||||||||||||||||
Funding support | China, 7items
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Citation | Journal: Cell Discov / Year: 2024 Title: Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Authors: Wenzhuo Li / Qingtong Zhou / Zhaotong Cong / Qingning Yuan / Wenxin Li / Fenghui Zhao / H Eric Xu / Li-Hua Zhao / Dehua Yang / Ming-Wei Wang / | ||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8yw5.cif.gz | 241.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8yw5.ent.gz | 184.9 KB | Display | PDB format |
PDBx/mmJSON format | 8yw5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8yw5_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8yw5_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8yw5_validation.xml.gz | 39.4 KB | Display | |
Data in CIF | 8yw5_validation.cif.gz | 59 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yw/8yw5 ftp://data.pdbj.org/pub/pdb/validation_reports/yw/8yw5 | HTTPS FTP |
-Related structure data
Related structure data | 39623MC 8yw3C 8yw4C 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 ABG
#3: Protein | Mass: 45683.434 Da / Num. of mol.: 1 Mutation: S54N, G226A, E268A, N271K, K274D, R280K, T284D, I285T Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63092 |
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#4: Protein | Mass: 37915.496 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 |
#5: 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 |
-Protein/peptide / Protein / Antibody , 3 types, 3 molecules PRN
#1: Protein/peptide | Mass: 3357.761 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) |
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#2: Protein | Mass: 46741.363 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GCGR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P47871 |
#6: Antibody | Mass: 15343.019 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Details
Has ligand of interest | Y |
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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: Cryo-EM structure of the retatrutide-bound human GCGR-Gs complex Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||
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: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 80 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: 2.84 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 554835 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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