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Yorodumi- EMDB-23101: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical... -
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Basic information
| Entry | Database: EMDB / ID: EMD-23101 | |||||||||
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| Title | Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, AHD and nanodisc mask out | |||||||||
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Keywords | GPCR / NTSR1 / NTS / G protein / Nanodisc / SIGNALING PROTEIN | |||||||||
| Function / homology | Function and homology informationregulation of locomotion involved in locomotory behavior / Peptide ligand-binding receptors / positive regulation of locomotion / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / regulation of inositol trisphosphate biosynthetic process / inositol phosphate catabolic process / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion ...regulation of locomotion involved in locomotory behavior / Peptide ligand-binding receptors / positive regulation of locomotion / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / regulation of inositol trisphosphate biosynthetic process / inositol phosphate catabolic process / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / eye photoreceptor cell development / regulation of membrane depolarization / positive regulation of arachidonate secretion / vocalization behavior / response to antipsychotic drug / neuron spine / L-glutamate import across plasma membrane / regulation of behavioral fear response / regulation of respiratory gaseous exchange / neuropeptide hormone activity / cAMP biosynthetic process / positive regulation of inhibitory postsynaptic potential / negative regulation of systemic arterial blood pressure / negative regulation of release of sequestered calcium ion into cytosol / digestive tract development / G alpha (q) signalling events / hyperosmotic response / positive regulation of glutamate secretion / response to mineralocorticoid / response to food / response to corticosterone / cellular response to lithium ion / temperature homeostasis / positive regulation of inositol phosphate biosynthetic process / response to lipid / response to stress / detection of temperature stimulus involved in sensory perception of pain / associative learning / conditioned place preference / phototransduction / neuropeptide signaling pathway / cellular response to dexamethasone stimulus / response to axon injury / adenylate cyclase inhibitor activity / transport vesicle / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / axon terminus / cardiac muscle cell apoptotic process / photoreceptor inner segment / cellular response to forskolin / regulation of mitotic spindle organization / positive regulation of release of sequestered calcium ion into cytosol / response to amphetamine / blood vessel diameter maintenance / dendritic shaft / adult locomotory behavior / learning / response to cocaine / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / liver development / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cellular response to nerve growth factor stimulus / visual learning / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / cytoplasmic side of plasma membrane / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / terminal bouton / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding Similarity search - Function | |||||||||
| Biological species | ![]() Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Zhang M / Gui M | |||||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2021Title: Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs. Authors: Meng Zhang / Miao Gui / Zi-Fu Wang / Christoph Gorgulla / James J Yu / Hao Wu / Zhen-Yu J Sun / Christoph Klenk / Lisa Merklinger / Lena Morstein / Franz Hagn / Andreas Plückthun / Alan ...Authors: Meng Zhang / Miao Gui / Zi-Fu Wang / Christoph Gorgulla / James J Yu / Hao Wu / Zhen-Yu J Sun / Christoph Klenk / Lisa Merklinger / Lena Morstein / Franz Hagn / Andreas Plückthun / Alan Brown / Mahmoud L Nasr / Gerhard Wagner / ![]() Abstract: G-protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been ...G-protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been solved for GPCR-G protein complexes, few are in a lipid membrane environment. Here, we report cryo-EM structures of complexes of neurotensin, neurotensin receptor 1 and Gαβγ in two conformational states, resolved to resolutions of 4.1 and 4.2 Å. The structures, determined in a lipid bilayer without any stabilizing antibodies or nanobodies, reveal an extended network of protein-protein interactions at the GPCR-G protein interface as compared to structures obtained in detergent micelles. The findings show that the lipid membrane modulates the structure and dynamics of complex formation and provide a molecular explanation for the stronger interaction between GPCRs and G proteins in lipid bilayers. We propose an allosteric mechanism for GDP release, providing new insights into the activation of G proteins for downstream signaling. | |||||||||
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Structure visualization
| Movie |
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| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
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Downloads & links
-EMDB archive
| Map data | emd_23101.map.gz | 58.9 MB | EMDB map data format | |
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| Header (meta data) | emd-23101-v30.xml emd-23101.xml | 22.5 KB 22.5 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_23101_fsc.xml | 9.2 KB | Display | FSC data file |
| Images | emd_23101.png | 110 KB | ||
| Masks | emd_23101_msk_1.map | 64 MB | Mask map | |
| Filedesc metadata | emd-23101.cif.gz | 6.4 KB | ||
| Others | emd_23101_half_map_1.map.gz emd_23101_half_map_2.map.gz | 49.9 MB 49.9 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23101 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23101 | HTTPS FTP |
-Validation report
| Summary document | emd_23101_validation.pdf.gz | 957.4 KB | Display | EMDB validaton report |
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| Full document | emd_23101_full_validation.pdf.gz | 957 KB | Display | |
| Data in XML | emd_23101_validation.xml.gz | 15.7 KB | Display | |
| Data in CIF | emd_23101_validation.cif.gz | 20.7 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23101 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23101 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7l0rMC ![]() 7l0pC ![]() 7l0qC ![]() 7l0sC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data |
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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_23101.map.gz / Format: CCP4 / Size: 64 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: 0.825 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_23101_msk_1.map | ||||||||||||
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-Half map: #1
| File | emd_23101_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #2
| File | emd_23101_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
+Entire : NTS-NTSR1-Gi complex in lipid nanodisc
+Supramolecule #1: NTS-NTSR1-Gi complex in lipid nanodisc
+Supramolecule #2: NTSR1
+Supramolecule #3: NTS
+Supramolecule #4: G(i) subunit alpha-1
+Supramolecule #5: G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #6: G(T) subunit gamma-1
+Macromolecule #1: Neurotensin receptor type 1
+Macromolecule #2: Neurotensin
+Macromolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #5: Guanine nucleotide-binding protein G(T) subunit gamma-T1
-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: 6.9 |
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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 BIOQUANTUM (6k x 4k) / Average electron dose: 57.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
| Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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| Output model | ![]() PDB-7l0r: |
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Keywords
Homo sapiens (human)
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