+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-12128 | |||||||||
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Title | AVP-V2R-Galphas-beta1-gamma2-Nb35 (L state) | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information 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 ...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 / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / 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 / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 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_12128.map.gz | 11.9 MB | EMDB map data format | |
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Header (meta data) | emd-12128-v30.xml emd-12128.xml | 28.8 KB 28.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_12128_fsc.xml | 12.2 KB | Display | FSC data file |
Images | emd_12128.png | 112 KB | ||
Masks | emd_12128_msk_1.map | 149.9 MB | Mask map | |
Others | emd_12128_additional_1.map.gz emd_12128_half_map_1.map.gz emd_12128_half_map_2.map.gz | 139.9 MB 118.3 MB 118.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-12128 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12128 | HTTPS FTP |
-Validation report
Summary document | emd_12128_validation.pdf.gz | 383.9 KB | Display | EMDB validaton report |
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Full document | emd_12128_full_validation.pdf.gz | 383.1 KB | Display | |
Data in XML | emd_12128_validation.xml.gz | 18.1 KB | Display | |
Data in CIF | emd_12128_validation.cif.gz | 22.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12128 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-12128 | HTTPS FTP |
-Related structure data
Related structure data | 7bb6MC 7bb7C 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_12128.map.gz / Format: CCP4 / Size: 12.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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_12128_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_12128_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_12128_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_12128_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : AVP-V2R-Galphas-beta1-gamma2-Nb35 (L state)
+Supramolecule #1: AVP-V2R-Galphas-beta1-gamma2-Nb35 (L state)
+Supramolecule #2: V2R and Guanine nucleotide-binding protein G(I)/G(S)/G(T)
+Supramolecule #3: arginine-vasopressin
+Supramolecule #4: Nanobody 35
+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: arginine-vasopressin
+Macromolecule #6: Nanobody 35
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4 mg/mL | ||||||||||||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR | ||||||||||||||||||||||||
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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Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | #0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #0 - Detector mode: COUNTING / #0 - Number grids imaged: 1 / #0 - Number real images: 17290 / #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 - Number grids imaged: 1 / #1 - Number real images: 8490 / #1 - Average electron dose: 50.19 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 / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 165000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 87.61 |
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Output model | PDB-7bb6: |