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Yorodumi- EMDB-23101: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical... -
+Open data
-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 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information response to antipsychotic drug / Peptide ligand-binding receptors / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / eye photoreceptor cell development / response to mineralocorticoid / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion ...response to antipsychotic drug / Peptide ligand-binding receptors / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / eye photoreceptor cell development / response to mineralocorticoid / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / regulation of membrane depolarization / positive regulation of arachidonate secretion / L-glutamate import across plasma membrane / neuron spine / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential / neuropeptide hormone activity / hyperosmotic response / digestive tract development / negative regulation of release of sequestered calcium ion into cytosol / negative regulation of systemic arterial blood pressure / G alpha (q) signalling events / positive regulation of glutamate secretion / positive regulation of inositol phosphate biosynthetic process / temperature homeostasis / response to corticosterone / response to lipid / cellular response to lithium ion / detection of temperature stimulus involved in sensory perception of pain / phototransduction / neuropeptide signaling pathway / response to axon injury / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / regulation of mitotic spindle organization / transport vesicle / cellular response to forskolin / cardiac muscle cell apoptotic process / response to amphetamine / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor inner segment / blood vessel diameter maintenance / cellular response to dexamethasone stimulus / adult locomotory behavior / positive regulation of release of sequestered calcium ion into cytosol / cellular response to nerve growth factor stimulus / liver development / learning / response to cocaine / dendritic shaft / Regulation of insulin secretion / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / visual learning / 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 / terminal bouton / 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 / cytoplasmic side of plasma membrane / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / 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 / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / protein localization / extracellular vesicle Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Zhang M / Gui M / Wang Z / Gorgulla C / Yu JJ / Wu H / Sun Z / Klenk C / Merklinger L / Morstein L ...Zhang M / Gui M / Wang Z / Gorgulla C / Yu JJ / Wu H / Sun Z / Klenk C / Merklinger L / Morstein L / Hagn F / Pluckthun A / Brown A / Nasr ML / Wagner G | |||||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: 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. | |||||||||
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_23101.map.gz | 58.9 MB | EMDB map data format | |
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Header (meta data) | emd-23101-v30.xml emd-23101.xml | 24.2 KB 24.2 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 | |
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 |
-Related structure data
Related structure data | 7l0rMC 7l0pC 7l0qC 7l0sC C: citing same article (ref.) M: atomic model generated by this map |
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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_23101.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_23101_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_23101_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-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 |
-Sample preparation
Buffer | pH: 6.9 |
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Vitrification | Cryogen name: ETHANE |
-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 |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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Output model | PDB-7l0r: |