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- EMDB-32095: Cryo-EM structure of human vasoactive intestinal polypeptide rece... -
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Open data
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Basic information
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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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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 | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.74 Å | ||||||||||||||||||
![]() | Xu YN / Feng WB / Zhou QT / Liang AY / Li J / Dai AT / Zhao FH / Yan JH / Chen CW / Li H ...Xu YN / Feng WB / Zhou QT / Liang AY / Li J / Dai AT / Zhao FH / Yan JH / Chen CW / Li H / Zhao LH / Xia T / Jiang Y / Xu HE / Yang DH / Wang MW | ||||||||||||||||||
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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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.2 KB 21.2 KB | Display Display | ![]() |
Images | ![]() | 16.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 435.9 KB | Display | ![]() |
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Full document | ![]() | 435.4 KB | Display | |
Data in XML | ![]() | 6.2 KB | Display | |
Data in CIF | ![]() | 7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vqxMC ![]() 7wbjC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.071 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Cryo-EM structure of the human vasoactive intestinal polypeptide ...
+Supramolecule #1: Cryo-EM structure of the human vasoactive intestinal polypeptide ...
+Supramolecule #2: human vasoactive intestinal polypeptide receptor 2
+Supramolecule #3: Pituitary adenylate cyclase activating peptide-27
+Supramolecule #4: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Supramolecule #5: Guanine nucleotide-binding protein G(I) /G(S) /G(T) subunit beta-1
+Supramolecule #6: Guanine nucleotide-binding protein G(I) /G(S) /G(O) subunit gamma-2
+Supramolecule #7: Nanobody-35
+Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Pituitary adenylate cyclase-activating polypeptide 27
+Macromolecule #5: Nanobody-35
+Macromolecule #6: Vasoactive intestinal polypeptide receptor 2
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.74 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES / Number images used: 602466 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |