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- PDB-7vqx: Cryo-EM structure of human vasoactive intestinal polypeptide rece... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7vqx | ||||||||||||||||||
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Title | Cryo-EM structure of human vasoactive intestinal polypeptide receptor 2 (VIP2R) in complex with PACAP27 and Gs | ||||||||||||||||||
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![]() | STRUCTURAL PROTEIN / vasoactive intestinal polypeptide receptor 2 / G protein-coupled receptor / ligand recognition | ||||||||||||||||||
Function / homology | ![]() pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / sensory perception of chemical stimulus / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade ...pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of growth hormone secretion / positive regulation of chemokine (C-C motif) ligand 5 production / sensory perception of chemical stimulus / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / G protein-coupled peptide receptor activity / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / alkylglycerophosphoethanolamine phosphodiesterase activity / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / insulin secretion / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / peptide hormone receptor binding / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / peptide hormone binding / negative regulation of cell cycle / mu-type opioid receptor binding / photoreceptor outer segment / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / positive regulation of protein kinase activity / neuropeptide signaling pathway / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / cardiac muscle cell apoptotic process / activation of adenylate cyclase activity / adenylate cyclase activator activity / photoreceptor inner segment / cAMP-mediated signaling / positive regulation of GTPase activity / G protein-coupled receptor activity / female pregnancy / negative regulation of smooth muscle cell proliferation / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Glucagon-type ligand receptors / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / regulation of protein localization / neuron projection development / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / cell-cell signaling / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / cell body / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() synthetic construct (others) ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.74 Å | ||||||||||||||||||
![]() | Xu, Y.N. / Feng, W.B. / Zhou, Q.T. / Liang, A.Y. / Li, J. / Dai, A.T. / Zhao, F.H. / Yan, J.H. / Chen, C.W. / Li, H. ...Xu, Y.N. / Feng, W.B. / Zhou, Q.T. / Liang, A.Y. / Li, J. / Dai, A.T. / Zhao, F.H. / Yan, J.H. / Chen, C.W. / Li, H. / Zhao, L.H. / Xia, T. / Jiang, Y. / Xu, H.E. / Yang, D.H. / Wang, M.W. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2. Authors: Yingna Xu / Wenbo Feng / Qingtong Zhou / Anyi Liang / Jie Li / Antao Dai / Fenghui Zhao / Jiahui Yan / Chuan-Wei Chen / Hao Li / Li-Hua Zhao / Tian Xia / Yi Jiang / H Eric Xu / Dehua Yang / Ming-Wei Wang / ![]() ![]() Abstract: Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is ...Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is expressed in the central and peripheral nervous systems and involved in a number of pathophysiological conditions, including pulmonary arterial hypertension, autoimmune and psychiatric disorders, in which it is thus a valuable drug target. Here, we report the cryo-electron microscopy structure of the human VIP2R bound to its endogenous ligand PACAP27 and the stimulatory G protein. Different from all reported peptide-bound class B1 GPCR structures, the N-terminal α-helix of VIP2R adopts a unique conformation that deeply inserts into a cleft between PACAP27 and the extracellular loop 1, thereby stabilizing the peptide-receptor interface. Its truncation or extension significantly decreased VIP2R-mediated cAMP accumulation. Our results provide additional information on peptide recognition and receptor activation among class B1 GPCRs and may facilitate the design of better therapeutics. | ||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 219.5 KB | Display | ![]() |
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PDB format | ![]() | 173 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 810.8 KB | Display | ![]() |
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Full document | ![]() | 822.1 KB | Display | |
Data in XML | ![]() | 35.3 KB | Display | |
Data in CIF | ![]() | 53.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 32095MC ![]() 7wbjC 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: 45743.441 Da / Num. of mol.: 1 Mutation: S54N, G226A, E268A, N271K, K274D, R280K, T284D, I285T, A366S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#2: Protein | Mass: 43706.750 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.) ![]() ![]() ![]() ![]() |
-Protein/peptide / Antibody / Protein , 3 types, 3 molecules LNR
#4: Protein/peptide | Mass: 3154.642 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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#5: 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: ![]() ![]() |
#6: Protein | Mass: 64579.445 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Details
Sequence details | The LgBit has been used for NanoBiT tethering strategy on B and R chains. |
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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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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
Software | Name: PHENIX / Version: 1.19.1_4122: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.74 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES / Num. of particles: 602466 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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