+Open data
-Basic information
Entry | Database: PDB / ID: 7p02 | |||||||||
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Title | Human Neurokinin 1 receptor (NK1R) substance P Gs complex | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Receptor / Complex / Eukaryotic protein | |||||||||
Function / homology | Function and homology information substance P receptor binding / substance P receptor activity / insemination / tachykinin receptor activity / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / detection of abiotic stimulus / positive regulation of synaptic transmission, cholinergic ...substance P receptor binding / substance P receptor activity / insemination / tachykinin receptor activity / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / detection of abiotic stimulus / positive regulation of synaptic transmission, cholinergic / tachykinin receptor signaling pathway / operant conditioning / positive regulation of lymphocyte proliferation / sperm head / response to ozone / sperm ejaculation / positive regulation of action potential / response to auditory stimulus / smooth muscle contraction involved in micturition / regulation of smooth muscle cell proliferation / positive regulation of hormone secretion / positive regulation of blood pressure / positive regulation of vascular permeability / positive regulation of ossification / regulation of smooth muscle cell migration / positive regulation of leukocyte migration / eating behavior / response to pain / positive regulation of epithelial cell migration / behavioral response to pain / associative learning / PKA activation in glucagon signalling / angiotensin-mediated drinking behavior / positive regulation of vasoconstriction / hair follicle placode formation / neuropeptide signaling pathway / developmental growth / D1 dopamine receptor binding / intracellular transport / sperm flagellum / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / Hedgehog 'off' state / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / long-term memory / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to electrical stimulus / positive regulation of epithelial cell proliferation / regulation of mitotic spindle organization / cellular response to forskolin / sperm midpiece / positive regulation of stress fiber assembly / sensory perception of pain / adenylate cyclase activator activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cellular response to nerve growth factor stimulus / trans-Golgi network membrane / Regulation of insulin secretion / response to progesterone / positive regulation of synaptic transmission, GABAergic / G protein-coupled receptor binding / response to nicotine / G-protein beta/gamma-subunit complex binding / bone development / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / platelet aggregation / 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 Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.87 Å | |||||||||
Authors | Thom, C. / Ehrenmann, J. / Vacca, S. / Waltenspuhl, Y. / Schoppe, J. / Medalia, O. / Pluckthun, A. | |||||||||
Funding support | Switzerland, 2items
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Citation | Journal: Sci Adv / Year: 2021 Title: Structures of neurokinin 1 receptor in complex with G and G proteins reveal substance P binding mode and unique activation features. Authors: Cristian Thom / Janosch Ehrenmann / Santiago Vacca / Yann Waltenspühl / Jendrik Schöppe / Ohad Medalia / Andreas Plückthun / Abstract: The neurokinin 1 receptor (NKR) is involved in inflammation and pain transmission. This pathophysiologically important G protein–coupled receptor is predominantly activated by its cognate agonist ...The neurokinin 1 receptor (NKR) is involved in inflammation and pain transmission. This pathophysiologically important G protein–coupled receptor is predominantly activated by its cognate agonist substance P (SP) but also by the closely related neurokinins A and B. Here, we report cryo–electron microscopy structures of SP-bound NKR in complex with its primary downstream signal mediators, G and G. Our structures reveal how a polar network at the extracellular, solvent-exposed receptor surface shapes the orthosteric pocket and that NKR adopts a noncanonical active-state conformation with an interface for G protein binding, which is distinct from previously reported structures. Detailed comparisons with antagonist-bound NKR crystal structures reveal that insurmountable antagonists induce a distinct and long-lasting receptor conformation that sterically blocks SP binding. Together, our structures provide important structural insights into ligand and G protein promiscuity, the lack of basal signaling, and agonist- and antagonist-induced conformations in the neurokinin receptor family. | |||||||||
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 | 7p02.cif.gz | 214.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7p02.ent.gz | 171.7 KB | Display | PDB format |
PDBx/mmJSON format | 7p02.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7p02_validation.pdf.gz | 644.2 KB | Display | wwPDB validaton report |
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Full document | 7p02_full_validation.pdf.gz | 652.3 KB | Display | |
Data in XML | 7p02_validation.xml.gz | 33 KB | Display | |
Data in CIF | 7p02_validation.cif.gz | 46.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p0/7p02 ftp://data.pdbj.org/pub/pdb/validation_reports/p0/7p02 | HTTPS FTP |
-Related structure data
Related structure data | 13141MC 7p00C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules BGA
#2: Protein | Mass: 39086.641 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 |
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#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
#4: Protein | Mass: 28428.365 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1, GNAS, GNAS1, GSP / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096, UniProt: P63092 |
-Antibody / Protein / Protein/peptide / Non-polymers , 4 types, 4 molecules HRP
#1: Antibody | Mass: 32409.229 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm) |
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#5: Protein | Mass: 44218.668 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TACR1, NK1R, TAC1R / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P25103 |
#6: Protein/peptide | Mass: 1348.637 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TAC1, NKA, NKNA, TAC2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P20366 |
#7: Chemical | ChemComp-CLR / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: NK1R in complex with Substance P, heterotrimeric mini-Gs chimera (Gsi) and scFv16 Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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 / Nominal magnification: 130000 X / Nominal defocus max: 2400 nm / Calibrated defocus min: 800 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 63.51 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.1_4122: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4227825 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.87 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 395052 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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