+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12129 | |||||||||
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Title | AVP-V2R-Galphas-beta1-gamma2-Nb35(T state) | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / hemostasis / positive regulation of systemic arterial blood pressure / telencephalon development / positive regulation of intracellular signal transduction / PKA activation in glucagon signalling ...renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / hemostasis / positive regulation of systemic arterial blood pressure / telencephalon development / positive regulation of intracellular signal transduction / PKA activation in glucagon signalling / positive regulation of vasoconstriction / hair follicle placode formation / endocytic vesicle / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to hormone stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / peptide binding / clathrin-coated endocytic vesicle membrane / response to cytokine / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / platelet aggregation / 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 / Cargo recognition for clathrin-mediated endocytosis / 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 / sensory perception of smell / Clathrin-mediated endocytosis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / endosome / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / lysosomal membrane / GTPase activity / positive regulation of cell population proliferation / synapse / positive regulation of gene expression / protein-containing complex binding / GTP binding / perinuclear region of cytoplasm / Golgi apparatus / signal transduction / endoplasmic reticulum / extracellular exosome / membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
Authors | Bous J / Mouillac B / Bron P / Granier S / Floquet N / Leyrat C | |||||||||
Funding support | France, 2 items
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Citation | Journal: Sci Adv / Year: 2021 Title: Cryo-electron microscopy structure of the antidiuretic hormone arginine-vasopressin V2 receptor signaling complex. Authors: Julien Bous / Hélène Orcel / Nicolas Floquet / Cédric Leyrat / Joséphine Lai-Kee-Him / Gérald Gaibelet / Aurélie Ancelin / Julie Saint-Paul / Stefano Trapani / Maxime Louet / Rémy ...Authors: Julien Bous / Hélène Orcel / Nicolas Floquet / Cédric Leyrat / Joséphine Lai-Kee-Him / Gérald Gaibelet / Aurélie Ancelin / Julie Saint-Paul / Stefano Trapani / Maxime Louet / Rémy Sounier / Hélène Déméné / Sébastien Granier / Patrick Bron / Bernard Mouillac / Abstract: The antidiuretic hormone arginine-vasopressin (AVP) forms a signaling complex with the V2 receptor (V2R) and the G protein, promoting kidney water reabsorption. Molecular mechanisms underlying ...The antidiuretic hormone arginine-vasopressin (AVP) forms a signaling complex with the V2 receptor (V2R) and the G protein, promoting kidney water reabsorption. Molecular mechanisms underlying activation of this critical G protein-coupled receptor (GPCR) signaling system are still unknown. To fill this gap of knowledge, we report here the cryo-electron microscopy structure of the AVP-V2R-G complex. Single-particle analysis revealed the presence of three different states. The two best maps were combined with computational and nuclear magnetic resonance spectroscopy constraints to reconstruct two structures of the ternary complex. These structures differ in AVP and G binding modes. They reveal an original receptor-G interface in which the Gα subunit penetrates deep into the active V2R. The structures help to explain how V2R R137H or R137L/C variants can lead to two severe genetic diseases. Our study provides important structural insights into the function of this clinically relevant GPCR signaling complex. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_12129.map.gz | 11.9 MB | EMDB map data format | |
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Header (meta data) | emd-12129-v30.xml emd-12129.xml | 32 KB 32 KB | Display Display | EMDB header |
Images | emd_12129.png | 112 KB | ||
Masks | emd_12129_msk_1.map | 18.7 MB | Mask map | |
Others | emd_12129_additional_1.map.gz emd_12129_additional_2.map.gz emd_12129_additional_3.map.gz emd_12129_half_map_1.map.gz emd_12129_half_map_2.map.gz | 17.5 MB 1.8 MB 2.2 MB 14.2 MB 14.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12129 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12129 | HTTPS FTP |
-Validation report
Summary document | emd_12129_validation.pdf.gz | 336.3 KB | Display | EMDB validaton report |
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Full document | emd_12129_full_validation.pdf.gz | 335.5 KB | Display | |
Data in XML | emd_12129_validation.xml.gz | 9 KB | Display | |
Data in CIF | emd_12129_validation.cif.gz | 9.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12129 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12129 | HTTPS FTP |
-Related structure data
Related structure data | 7bb7MC 7bb6C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_12129.map.gz / Format: CCP4 / Size: 12.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 0.81 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_12129_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #3
File | emd_12129_additional_1.map | ||||||||||||
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Density Histograms |
-Additional map: #2
File | emd_12129_additional_2.map | ||||||||||||
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Density Histograms |
-Additional map: #1
File | emd_12129_additional_3.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_12129_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_12129_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
+Entire : AVP-V2R-Galphas-beta1-gamma2-Nb35(T state)
+Supramolecule #1: AVP-V2R-Galphas-beta1-gamma2-Nb35(T state)
+Supramolecule #2: V2R and Guanine nucleotide-binding protein G(I)/G(S)/G(T)
+Supramolecule #3: Nanobody 35
+Supramolecule #4: Vasopressin
+Macromolecule #1: Vasopressin V2 receptor
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: Nanobody 35
+Macromolecule #6: Vasopressin
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK III |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | #0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #0 - Detector mode: COUNTING / #0 - Average electron dose: 41.19 e/Å2 / #1 - Image recording ID: 2 / #1 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #1 - Detector mode: COUNTING / #1 - Average electron dose: 41.19 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |