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Yorodumi- EMDB-13140: Human Neurokinin 1 receptor (NK1R) substance P Gq chimera (mGsqi)... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13140 | |||||||||
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Title | Human Neurokinin 1 receptor (NK1R) substance P Gq chimera (mGsqi) complex | |||||||||
Map data | processed map | |||||||||
Sample |
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Function / homology | Function and homology information substance P receptor activity / 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 ...substance P receptor activity / 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 / positive regulation of epithelial cell migration / behavioral response to pain / associative learning / angiotensin-mediated drinking behavior / positive regulation of vasoconstriction / sperm flagellum / 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 / long-term memory / 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 / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / 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 / 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 / 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 / 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 / Cargo recognition for clathrin-mediated endocytosis / 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 / extracellular vesicle / Clathrin-mediated endocytosis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / response to estradiol / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.71 Å | |||||||||
Authors | Thom C / Ehrenmann J / Vacca S / Waltenspuhl Y / Schoppe J / Medalia O / Pluckthun A | |||||||||
Funding support | Switzerland, 2 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_13140.map.gz | 258.7 MB | EMDB map data format | |
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Header (meta data) | emd-13140-v30.xml emd-13140.xml | 20.5 KB 20.5 KB | Display Display | EMDB header |
Images | emd_13140.png | 47.4 KB | ||
Others | emd_13140_additional_1.map.gz | 135.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13140 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13140 | HTTPS FTP |
-Validation report
Summary document | emd_13140_validation.pdf.gz | 340.5 KB | Display | EMDB validaton report |
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Full document | emd_13140_full_validation.pdf.gz | 340.1 KB | Display | |
Data in XML | emd_13140_validation.xml.gz | 7.3 KB | Display | |
Data in CIF | emd_13140_validation.cif.gz | 8.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13140 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13140 | HTTPS FTP |
-Related structure data
Related structure data | 7p00MC 7p02C M: atomic model generated by this map C: citing same article (ref.) |
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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_13140.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | processed map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.651 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: raw map
File | emd_13140_additional_1.map | ||||||||||||
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Annotation | raw map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : NK1R in complex with Substance P, heterotrimeric mini-Gq chimera ...
Entire | Name: NK1R in complex with Substance P, heterotrimeric mini-Gq chimera (Gsqi) and scFv16 |
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Components |
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-Supramolecule #1: NK1R in complex with Substance P, heterotrimeric mini-Gq chimera ...
Supramolecule | Name: NK1R in complex with Substance P, heterotrimeric mini-Gq chimera (Gsqi) and scFv16 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: Antibody fragment scFv16
Macromolecule | Name: Antibody fragment scFv16 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 32.409229 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPDVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPE KGLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG Q GTTLTVSS ...String: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPDVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPE KGLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG Q GTTLTVSS GGGGSGGGGS GGGGSDIVMT QATSSVPVTP GESVSISCRS SKSLLHSNGN TYLYWFLQRP GQSPQLLIYR MS NLASGVP DRFSGSGSGT AFTLTISRLE AEDVGVYYCM QHLEYPLTFG AGTKLELKAA A |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 39.086641 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MHHHHHHHHH HGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY L SCCRFLDD ...String: MHHHHHHHHH HGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY L SCCRFLDD NQIVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HE SDINAIC FFPNGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAG VLAGHD NRVSCLGVTD DGMAVATGSW DSFLKIWN |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine n...
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 28.304219 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNLFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...String: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNLFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENARRIF NDCKDIILQM NL REYNLV |
-Macromolecule #5: Substance-P receptor
Macromolecule | Name: Substance-P receptor / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 44.218668 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPMDN VLPVDSDLSP NISTNTSEPN QFVQPAWQIV LWAAAYTVI VVTSVVGNVV VMWIILAHKR MRTVTNYFLV NLAFAEASMA AFNTVVNFTY AVHNEWYYGL FYCKFHNFFP I AAVFASIY ...String: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPMDN VLPVDSDLSP NISTNTSEPN QFVQPAWQIV LWAAAYTVI VVTSVVGNVV VMWIILAHKR MRTVTNYFLV NLAFAEASMA AFNTVVNFTY AVHNEWYYGL FYCKFHNFFP I AAVFASIY SMTAVAFDRY MAIIHPLQPR LSATATKVVI CVIWVLALLL AFPQGYYSTT ETMPSRVVCM IEWPEHPNKI YE KVYHICV TVLIYFLPLL VIGYAYTVVG ITLWASEIPG DSSDRYHEQV SAKRKVVKMM IVVVCTFAIC WLPFHIFFLL PYI NPDLYL KKFIQQVYLA IMWLAMSSTM YNPIIYCCLN DRFRLGFKHA FRCCPFISAG DYEGLE |
-Macromolecule #6: Substance P
Macromolecule | Name: Substance P / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 1.348637 KDa |
Sequence | String: RPKPQQFFGL M(NH2) |
-Macromolecule #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 1 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-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: 62.51 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated defocus min: 0.8 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal magnification: 130000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |