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Yorodumi- EMDB-32401: N-terminal modified human vasoactive intestinal polypeptide recep... -
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Basic information
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| Title | N-terminal modified human vasoactive intestinal polypeptide receptor 2 (VIP2R) in complex with PACAP27 and Gs | ||||||||||||||||||
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Keywords | vasoactive intestinal polypeptide receptor 2 / G protein-coupled receptor / ligand recognition / STRUCTURAL PROTEIN | ||||||||||||||||||
| Function / homology | Function and homology informationpituitary adenylate cyclase activating polypeptide activity / type 1 vasoactive intestinal polypeptide receptor binding / type 2 vasoactive intestinal polypeptide receptor binding / pituitary adenylate cyclase-activating polypeptide receptor 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 / mu-type opioid receptor binding ...pituitary adenylate cyclase activating polypeptide activity / type 1 vasoactive intestinal polypeptide receptor binding / type 2 vasoactive intestinal polypeptide receptor binding / pituitary adenylate cyclase-activating polypeptide receptor 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 / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / neuropeptide hormone activity / regulation of G protein-coupled receptor signaling pathway / 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 / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G protein-coupled peptide receptor activity / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / beta-2 adrenergic receptor binding / 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 / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / insulin secretion / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (z) signalling events / Extra-nuclear estrogen signaling / photoreceptor outer segment membrane / G alpha (s) signalling events / G alpha (q) signalling events / spectrin binding / G alpha (i) signalling events / peptide hormone receptor binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / alkylglycerophosphoethanolamine phosphodiesterase activity / negative regulation of cell cycle / positive regulation of protein kinase activity / peptide hormone binding / positive regulation of GTPase activity / photoreceptor outer segment / neuropeptide signaling pathway / D1 dopamine receptor binding / activation of adenylate cyclase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / insulin-like growth factor receptor binding / cardiac muscle cell apoptotic process / photoreceptor inner segment / ionotropic glutamate receptor binding / adenylate cyclase activator activity / female pregnancy / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuron projection development / Glucagon-type ligand receptors / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cell-cell signaling / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of taste / regulation of protein localization / signaling receptor complex adaptor activity / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / positive regulation of cytosolic calcium ion concentration / cell body Similarity search - Function | ||||||||||||||||||
| Biological species | Homo sapiens (human) / ![]() ![]() | ||||||||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.42 Å | ||||||||||||||||||
Authors | 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 | ||||||||||||||||||
| Funding support | China, 5 items
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Citation | Journal: Nat Commun / Year: 2022Title: 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. | ||||||||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_32401.map.gz | 85.9 MB | EMDB map data format | |
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| Header (meta data) | emd-32401-v30.xml emd-32401.xml | 22.2 KB 22.2 KB | Display Display | EMDB header |
| Images | emd_32401.png | 21.2 KB | ||
| Filedesc metadata | emd-32401.cif.gz | 7.1 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32401 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32401 | HTTPS FTP |
-Validation report
| Summary document | emd_32401_validation.pdf.gz | 459.2 KB | Display | EMDB validaton report |
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| Full document | emd_32401_full_validation.pdf.gz | 458.7 KB | Display | |
| Data in XML | emd_32401_validation.xml.gz | 6.4 KB | Display | |
| Data in CIF | emd_32401_validation.cif.gz | 7.4 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32401 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32401 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7wbjMC ![]() 7vqxC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_32401.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| 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: Vasoactive intestinal polypeptide receptor 2
+Supramolecule #3: Pituitary adenylate cyclase-activating polypeptide 27
+Supramolecule #4: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Supramolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #6: Nanobody-35
+Macromolecule #1: Vasoactive intestinal polypeptide receptor 2
+Macromolecule #2: Pituitary adenylate cyclase-activating polypeptide 27
+Macromolecule #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: Nanobody-35
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | 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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About Yorodumi



Keywords
Homo sapiens (human)
Authors
China, 5 items
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