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Open data
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Basic information
Entry | Database: PDB / ID: 8yw5 | ||||||||||||||||||||||||
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Title | Cryo-EM structure of the retatrutide-bound human GCGR-Gs complex | ||||||||||||||||||||||||
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![]() | STRUCTURAL PROTEIN / G protein-coupled receptor / ligand recognition / receptor activation / unimolecular agonist / retatrutide | ||||||||||||||||||||||||
Function / homology | ![]() regulation of glycogen metabolic process / glucagon receptor activity / cellular response to glucagon stimulus / response to starvation / exocytosis / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding ...regulation of glycogen metabolic process / glucagon receptor activity / cellular response to glucagon stimulus / response to starvation / exocytosis / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / generation of precursor metabolites and energy / hormone-mediated signaling pathway / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to nutrient / adenylate cyclase activator activity / cellular response to starvation / guanyl-nucleotide exchange factor activity / trans-Golgi network membrane / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / platelet aggregation / 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 / 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 / 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 / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / glucose homeostasis / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / 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 / Extra-nuclear estrogen signaling / cell population proliferation / endosome / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / positive regulation of gene expression / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() synthetic construct (others) | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.84 Å | ||||||||||||||||||||||||
![]() | 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 | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 241.8 KB | Display | ![]() |
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PDB format | ![]() | 184.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 39.4 KB | Display | |
Data in CIF | ![]() | 59 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 39623MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 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.) ![]() ![]() ![]() |
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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.) ![]() ![]() ![]() |
#5: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-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.) ![]() ![]() ![]() |
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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.) ![]() ![]() ![]() |
#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: ![]() ![]() |
-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 |
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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 |
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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: 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) |
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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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