[English] 日本語

- EMDB-23101: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical... -
+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-23101 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of NTS-NTSR1-Gi complex in lipid nanodisc, noncanonical state, AHD and nanodisc mask out | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | GPCR / NTSR1 / NTS / G protein / Nanodisc / SIGNALING PROTEIN | |||||||||
Function / homology | ![]() response to antipsychotic drug / Peptide ligand-binding receptors / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / response to mineralocorticoid / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / eye photoreceptor cell development ...response to antipsychotic drug / Peptide ligand-binding receptors / neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / symmetric synapse / response to mineralocorticoid / 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 / neuron spine / L-glutamate import across plasma membrane / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential / neuropeptide hormone activity / hyperosmotic response / negative regulation of systemic arterial blood pressure / positive regulation of glutamate secretion / negative regulation of release of sequestered calcium ion into cytosol / G alpha (q) signalling events / digestive tract development / response to corticosterone / positive regulation of inositol phosphate biosynthetic process / cellular response to lithium ion / response to lipid / temperature homeostasis / detection of temperature stimulus involved in sensory perception of pain / phototransduction / response to axon injury / neuropeptide signaling pathway / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / T cell migration / transport vesicle / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / axon terminus / photoreceptor inner segment / cardiac muscle cell apoptotic process / cellular response to forskolin / response to amphetamine / regulation of mitotic spindle organization / cellular response to dexamethasone stimulus / dendritic shaft / positive regulation of release of sequestered calcium ion into cytosol / blood vessel diameter maintenance / liver development / adult locomotory behavior / learning / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / response to cocaine / G protein-coupled receptor binding / centriolar satellite / cellular response to nerve growth factor stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / terminal bouton / visual learning / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / response to peptide hormone / 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 / 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 / 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / protein localization / cellular response to prostaglandin E stimulus Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
![]() | Zhang M / Gui M | |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 58.9 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 22.5 KB 22.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.2 KB | Display | ![]() |
Images | ![]() | 110 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 6.4 KB | ||
Others | ![]() ![]() | 49.9 MB 49.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 957.4 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 957 KB | Display | |
Data in XML | ![]() | 15.7 KB | Display | |
Data in CIF | ![]() | 20.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7l0rMC ![]() 7l0pC ![]() 7l0qC ![]() 7l0sC C: citing same article ( M: atomic model generated by this map |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_23101_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_23101_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
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 |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 6.9 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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: ![]() |
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 |
---|---|
Output model | ![]() PDB-7l0r: |