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Open data
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Basic information
Entry | Database: PDB / ID: 7xz6 | ||||||
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Title | GPR119-Gs-APD668 complex | ||||||
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![]() | MEMBRANE PROTEIN / GPCR / Glucose-dependent insulinotropic receptor / GPR119 / LysoPC / Lysophosphatidylcholine / APD668 / G-protein / Gs / signaling complex / cryo-EM structure / structure-function relationships | ||||||
Function / homology | ![]() Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / phosphatidylcholine binding / regulation of metabolic process / insulin secretion / G protein-coupled receptor activity / electron transport chain / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors ...Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / phosphatidylcholine binding / regulation of metabolic process / insulin secretion / G protein-coupled receptor activity / electron transport chain / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / receptor complex / iron ion binding / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / heme binding / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
![]() | Xu, P. / Huang, S. / Jiang, Y. / Xu, H.E. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural identification of lysophosphatidylcholines as activating ligands for orphan receptor GPR119. Authors: Peiyu Xu / Sijie Huang / Shimeng Guo / Ying Yun / Xi Cheng / Xinheng He / Pengjun Cai / Yuan Lan / Hu Zhou / Hualiang Jiang / Yi Jiang / Xin Xie / H Eric Xu / ![]() ![]() Abstract: Lysophosphatidylcholine (LPC) is an essential mediator in human lipid metabolism and is associated with a variety of diseases, but the exact identity of LPC receptors remains controversial. Through ...Lysophosphatidylcholine (LPC) is an essential mediator in human lipid metabolism and is associated with a variety of diseases, but the exact identity of LPC receptors remains controversial. Through extensive biochemical and structural analyses, we have identified the orphan receptor GPR119 as the receptor for LPC. The structure of the GPR119-G-protein complex without any added ligands reveals a density map that fits well with LPC, which is further confirmed by mass spectrometry and functional studies. As LPCs are abundant on the cell membrane, their preoccupancy in the receptor may lead to 'constitutive activity' of GPR119. The structure of GPR119 bound to APD668, a clinical drug candidate for type 2 diabetes, reveals an exceedingly similar binding mode to LPC. Together, these data highlight structural evidence for LPC function in regulating glucose-dependent insulin secretion through direct binding and activation of GPR119, and provide structural templates for drug design targeting GPR119. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 355.5 KB | Display | ![]() |
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PDB format | ![]() | 289 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 | ![]() | 38 KB | Display | |
Data in CIF | ![]() | 56 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 33526MC ![]() 7xz5C 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
#1: Protein | Mass: 45699.434 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 37915.496 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Antibody / Protein , 2 types, 2 molecules NR
#4: Antibody | Mass: 15271.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#5: Protein | Mass: 53785.129 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: cybC, GPR119 / Production host: ![]() |
-Non-polymers , 2 types, 2 molecules ![](data/chem/img/I7J.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/HOH.gif)
#6: Chemical | ChemComp-I7J / |
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#7: Water | ChemComp-HOH / |
-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
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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-PROPANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 515782 / Symmetry type: POINT | ||||||||||||||||||||||||
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