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Yorodumi- PDB-7l0q: Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical st... -
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-Basic information
Entry | Database: PDB / ID: 7l0q | ||||||
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Title | Structure of NTS-NTSR1-Gi complex in lipid nanodisc, canonical state, with AHD | ||||||
Components |
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Keywords | SIGNALING PROTEIN / GPCR / NTSR1 / NTS / G protein / Nanodisc | ||||||
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 / response to lipid / 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 / 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 / cellular response to dexamethasone stimulus / 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 / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.3 Å | ||||||
Authors | Zhang, M. / Gui, M. / Wang, Z. / Gorgulla, C. / Yu, J.J. / Wu, H. / Sun, Z. / Klenk, C. / Merklinger, L. / Morstein, L. ...Zhang, M. / Gui, M. / Wang, Z. / Gorgulla, C. / Yu, J.J. / Wu, H. / Sun, Z. / Klenk, C. / Merklinger, L. / Morstein, L. / Hagn, F. / Pluckthun, A. / Brown, A. / Nasr, M.L. / 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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7l0q.cif.gz | 205.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7l0q.ent.gz | 166.1 KB | Display | PDB format |
PDBx/mmJSON format | 7l0q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7l0q_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7l0q_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7l0q_validation.xml.gz | 41.9 KB | Display | |
Data in CIF | 7l0q_validation.cif.gz | 62.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l0/7l0q ftp://data.pdbj.org/pub/pdb/validation_reports/l0/7l0q | HTTPS FTP |
-Related structure data
Related structure data | 23100MC 7l0pC 7l0rC 7l0sC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 37483.016 Da / Num. of mol.: 1 Mutation: A86L, H103D, H105Y, A161V, R213L, V234L, I253A, H305R, F358V, S362A, del273-290 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Ntsr1, Ntsr / Production host: Escherichia coli (E. coli) / References: UniProt: P20789 |
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#2: Protein/peptide | Mass: 1087.277 Da / Num. of mol.: 1 / Fragment: residues 157-162 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Nts / Production host: Escherichia coli (E. coli) / References: UniProt: P20068 |
#3: Protein | Mass: 40415.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096 |
#4: Protein | Mass: 39983.727 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 |
#5: Protein | Mass: 9593.011 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNGT1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63211 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight |
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Source (recombinant) |
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Buffer solution | pH: 6.9 | ||||||||||||||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 57 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4367542 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 575791 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL |