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Yorodumi- EMDB-20181: human Neurotensin Receptor 1 (hNTSR1) - Gi1 Protein Complex in no... -
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-Basic information
Entry | Database: EMDB / ID: EMD-20181 | |||||||||||||||||||||
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Title | human Neurotensin Receptor 1 (hNTSR1) - Gi1 Protein Complex in non-canonical conformation (NC state) | |||||||||||||||||||||
Map data | human neurotensin receptor 1 (hNTSR1) - Gi1 complex in non-canonical conformation (NC state) | |||||||||||||||||||||
Sample |
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Function / homology | Function and homology information G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / positive regulation of inhibitory postsynaptic potential / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / L-glutamate import across plasma membrane / positive regulation of arachidonic acid secretion / regulation of respiratory gaseous exchange / negative regulation of systemic arterial blood pressure ...G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / positive regulation of inhibitory postsynaptic potential / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / L-glutamate import across plasma membrane / positive regulation of arachidonic acid secretion / regulation of respiratory gaseous exchange / negative regulation of systemic arterial blood pressure / negative regulation of release of sequestered calcium ion into cytosol / positive regulation of glutamate secretion / positive regulation of inositol phosphate biosynthetic process / temperature homeostasis / response to lipid / detection of temperature stimulus involved in sensory perception of pain / regulation of membrane depolarization / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / cell cortex region / neuropeptide signaling pathway / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / adult locomotory behavior / positive regulation of release of sequestered calcium ion into cytosol / dendritic shaft / learning / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / terminal bouton / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / cytoplasmic side of plasma membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / response to peptide hormone / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / cellular response to prostaglandin E stimulus / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / G alpha (i) signalling events / fibroblast proliferation / midbody / chemical synaptic transmission / perikaryon / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / dendritic spine / cell cycle / G protein-coupled receptor signaling pathway / positive regulation of apoptotic process / membrane raft / lysosomal membrane Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||||||||||||||
Authors | Kato HE / Zhang Y / Kobilka BK / Skiniotis G | |||||||||||||||||||||
Funding support | Japan, United States, Denmark, 6 items
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Citation | Journal: Nature / Year: 2019 Title: Conformational transitions of a neurotensin receptor 1-G complex. Authors: Hideaki E Kato / Yan Zhang / Hongli Hu / Carl-Mikael Suomivuori / Francois Marie Ngako Kadji / Junken Aoki / Kaavya Krishna Kumar / Rasmus Fonseca / Daniel Hilger / Weijiao Huang / Naomi R ...Authors: Hideaki E Kato / Yan Zhang / Hongli Hu / Carl-Mikael Suomivuori / Francois Marie Ngako Kadji / Junken Aoki / Kaavya Krishna Kumar / Rasmus Fonseca / Daniel Hilger / Weijiao Huang / Naomi R Latorraca / Asuka Inoue / Ron O Dror / Brian K Kobilka / Georgios Skiniotis / Abstract: Neurotensin receptor 1 (NTSR1) is a G-protein-coupled receptor (GPCR) that engages multiple subtypes of G protein, and is involved in the regulation of blood pressure, body temperature, weight and ...Neurotensin receptor 1 (NTSR1) is a G-protein-coupled receptor (GPCR) that engages multiple subtypes of G protein, and is involved in the regulation of blood pressure, body temperature, weight and the response to pain. Here we present structures of human NTSR1 in complex with the agonist JMV449 and the heterotrimeric G protein, at a resolution of 3 Å. We identify two conformations: a canonical-state complex that is similar to recently reported GPCR-G complexes (in which the nucleotide-binding pocket adopts more flexible conformations that may facilitate nucleotide exchange), and a non-canonical state in which the G protein is rotated by about 45 degrees relative to the receptor and exhibits a more rigid nucleotide-binding pocket. In the non-canonical state, NTSR1 exhibits features of both active and inactive conformations, which suggests that the structure may represent an intermediate form along the activation pathway of G proteins. This structural information, complemented by molecular dynamics simulations and functional studies, provides insights into the complex process of G-protein activation. | |||||||||||||||||||||
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_20181.map.gz | 49.4 MB | EMDB map data format | |
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Header (meta data) | emd-20181-v30.xml emd-20181.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
Images | emd_20181.png | 93.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20181 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20181 | HTTPS FTP |
-Related structure data
Related structure data | 6osaMC 6os9C 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_20181.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | human neurotensin receptor 1 (hNTSR1) - Gi1 complex in non-canonical conformation (NC state) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : hNTSR1-Gi1 complex in non-canonical conformation (NC state)
Entire | Name: hNTSR1-Gi1 complex in non-canonical conformation (NC state) |
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Components |
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-Supramolecule #1: hNTSR1-Gi1 complex in non-canonical conformation (NC state)
Supramolecule | Name: hNTSR1-Gi1 complex in non-canonical conformation (NC state) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: Neurotensin receptor type 1
Macromolecule | Name: Neurotensin receptor type 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 48.396734 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DYKDDDDAMG QPGNGSAFLL APNRSHAPDH DVENLYFQGQ RAQAGLEEAL LAPGFGNASG NASERVLAAP SSELDVNTDI YSKVLVTAV YLALFVVGTV GNTVTLFTLA RKKSLQSLQS TVHYHLGSLA LSDLLTLLLA MPVELYNFIW VHHPWAFGDA G CRGYYFLR ...String: DYKDDDDAMG QPGNGSAFLL APNRSHAPDH DVENLYFQGQ RAQAGLEEAL LAPGFGNASG NASERVLAAP SSELDVNTDI YSKVLVTAV YLALFVVGTV GNTVTLFTLA RKKSLQSLQS TVHYHLGSLA LSDLLTLLLA MPVELYNFIW VHHPWAFGDA G CRGYYFLR DACTYATALN VASLSVERYL AICHPFKAKT LMSRSRTKKF ISAIWLASAL LAVPMLFTMG EQNRSADGQH AG GLVCTPT IHTATVKVVI QVNTFMSFIF PMVVISVLNT IIANKLTVMV RQAAEQGQVC TVGGPGRVQA LRHGVRVLRA VVI AFVVCW LPYHVRRLMF CYISDEQWTP FLYDFYHYFY MVTNALFYVS STINPILYNL VSANFRHIFL ATLACLCPVW RRRR KRPAF SRKADSVSSN HTLSSNATRE TLYLEVLFQG |
-Macromolecule #2: JMV449
Macromolecule | Name: JMV449 / type: protein_or_peptide / ID: 2 / Details: JMV449 from Tocris Bioscience. / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 762.979 Da |
Sequence | String: KKPYIL |
-Macromolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 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: 40.415031 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.671102 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT ...String: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HESDINAICF FP NGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAGVLAGHDN RVS CLGVTD DGMAVATGSW DSFLKIWN |
-Macromolecule #5: 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: 5 / 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: Trichoplusia ni (cabbage looper) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 10.0 sec. / Average electron dose: 75.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: Details: 4XEE and 1GP2 were used. |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 207119 |