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Yorodumi- PDB-6vn7: Cryo-EM structure of an activated VIP1 receptor-G protein complex -
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-Basic information
Entry | Database: PDB / ID: 6vn7 | |||||||||
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Title | Cryo-EM structure of an activated VIP1 receptor-G protein complex | |||||||||
Components |
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Keywords | SIGNALING PROTEIN / Vasoactive intestinal polypeptide receptor / VIP1R / G protein-coupled receptor / Gs protein / cryo-EM structure | |||||||||
Function / homology | Function and homology information pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of growth hormone secretion / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / G protein-coupled peptide receptor activity / insulin secretion / peptide hormone receptor binding ...pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of growth hormone secretion / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / G protein-coupled peptide receptor activity / insulin secretion / peptide hormone receptor binding / activation of adenylate cyclase activity / peptide hormone binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / negative regulation of cell cycle / neuropeptide signaling pathway / positive regulation of protein kinase activity / cAMP-mediated signaling / positive regulation of GTPase activity / female pregnancy / 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 / 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 / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / neuron projection development / positive regulation of cold-induced thermogenesis / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / cell-cell signaling / GTPase binding / regulation of protein localization / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / perikaryon / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / receptor complex / cell surface receptor signaling pathway / neuron projection / G protein-coupled receptor signaling pathway / lysosomal membrane / signaling receptor binding / GTPase activity / positive regulation of cell population proliferation / synapse / protein-containing complex binding / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular exosome / extracellular region / 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: 3.2 Å | |||||||||
Authors | Duan, J. / Shen, D.-D. / Zhou, X.E. / Liu, Q.-F. / Zhuang, Y.-W. / Zhang, H.-B. / Xu, P.-Y. / Ma, S.-S. / He, X.-H. / Melcher, K. ...Duan, J. / Shen, D.-D. / Zhou, X.E. / Liu, Q.-F. / Zhuang, Y.-W. / Zhang, H.-B. / Xu, P.-Y. / Ma, S.-S. / He, X.-H. / Melcher, K. / Zhang, Y. / Xu, H.E. / Yi, J. | |||||||||
Funding support | China, 2items
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Citation | Journal: Nat Commun / Year: 2020 Title: Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy. Authors: Jia Duan / Dan-Dan Shen / X Edward Zhou / Peng Bi / Qiu-Feng Liu / Yang-Xia Tan / You-Wen Zhuang / Hui-Bing Zhang / Pei-Yu Xu / Si-Jie Huang / Shan-Shan Ma / Xin-Heng He / Karsten Melcher / ...Authors: Jia Duan / Dan-Dan Shen / X Edward Zhou / Peng Bi / Qiu-Feng Liu / Yang-Xia Tan / You-Wen Zhuang / Hui-Bing Zhang / Pei-Yu Xu / Si-Jie Huang / Shan-Shan Ma / Xin-Heng He / Karsten Melcher / Yan Zhang / H Eric Xu / Yi Jiang / Abstract: Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. ...Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6vn7.cif.gz | 232.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6vn7.ent.gz | 185.3 KB | Display | PDB format |
PDBx/mmJSON format | 6vn7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6vn7_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6vn7_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6vn7_validation.xml.gz | 34.3 KB | Display | |
Data in CIF | 6vn7_validation.cif.gz | 51.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vn/6vn7 ftp://data.pdbj.org/pub/pdb/validation_reports/vn/6vn7 | HTTPS FTP |
-Related structure data
Related structure data | 21249MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-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: 45727.441 Da / Num. of mol.: 1 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: 41055.867 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 / Protein/peptide / Antibody , 3 types, 3 molecules RLN
#1: Protein | Mass: 66245.188 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: VIPR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P32241*PLUS |
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#2: Protein/peptide | Mass: 3154.642 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P18509 |
#6: Antibody | Mass: 14714.320 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) |
-Non-polymers , 2 types, 10 molecules
#7: Chemical | ChemComp-CLR / #8: Chemical | ChemComp-PLM / |
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-Details
Has ligand of interest | N |
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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: PACAP27-VIP1R-Gs protein complex stabilized by Nanobody 35 and NanoBiT system Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 8 |
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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 131263 / Symmetry type: POINT |