+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20836 | |||||||||
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Title | neurotensin receptor and arrestin2 complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / angiotensin receptor binding / positive regulation of inhibitory postsynaptic potential / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / Activation of SMO / negative regulation of interleukin-8 production ...neuropeptide receptor binding / G protein-coupled neurotensin receptor activity / inositol phosphate catabolic process / angiotensin receptor binding / positive regulation of inhibitory postsynaptic potential / symmetric synapse / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / Activation of SMO / negative regulation of interleukin-8 production / L-glutamate import across plasma membrane / positive regulation of arachidonic acid secretion / regulation of respiratory gaseous exchange / neuropeptide hormone activity / negative regulation of systemic arterial blood pressure / arrestin family protein binding / G protein-coupled receptor internalization / negative regulation of release of sequestered calcium ion into cytosol / enzyme inhibitor activity / positive regulation of glutamate secretion / positive regulation of inositol phosphate biosynthetic process / Lysosome Vesicle Biogenesis / temperature homeostasis / positive regulation of Rho protein signal transduction / Golgi Associated Vesicle Biogenesis / response to lipid / detection of temperature stimulus involved in sensory perception of pain / negative regulation of NF-kappaB transcription factor activity / regulation of membrane depolarization / stress fiber assembly / negative regulation of Notch signaling pathway / pseudopodium / negative regulation of interleukin-6 production / positive regulation of receptor internalization / neuropeptide signaling pathway / axon terminus / clathrin-coated pit / transport vesicle / insulin-like growth factor receptor binding / visual perception / blood vessel diameter maintenance / Activated NOTCH1 Transmits Signal to the Nucleus / GTPase activator activity / Peptide ligand-binding receptors / negative regulation of protein ubiquitination / adult locomotory behavior / positive regulation of release of sequestered calcium ion into cytosol / dendritic shaft / learning / G protein-coupled receptor binding / G protein-coupled receptor activity / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / cytoplasmic vesicle membrane / terminal bouton / cytoplasmic side of plasma membrane / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / protein transport / Signaling by BRAF and RAF1 fusions / Thrombin signalling through proteinase activated receptors (PARs) / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / positive regulation of NF-kappaB transcription factor activity / ubiquitin-dependent protein catabolic process / chemical synaptic transmission / perikaryon / cytoplasmic vesicle / G alpha (s) signalling events / G alpha (q) signalling events / proteasome-mediated ubiquitin-dependent protein catabolic process / dendritic spine / transcription coactivator activity / receptor ligand activity / positive regulation of ERK1 and ERK2 cascade / nuclear body / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein ubiquitination / Ub-specific processing proteases / G protein-coupled receptor signaling pathway / positive regulation of apoptotic process / membrane raft / positive regulation of protein phosphorylation / lysosomal membrane / Golgi membrane / negative regulation of gene expression / intracellular membrane-bounded organelle / chromatin / ubiquitin protein ligase binding / protein-containing complex binding / positive regulation of gene expression / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / signal transduction / positive regulation of transcription by RNA polymerase II Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Qu QH / Huang W / Masureel M / Janetzko J / Kobilka BK / Skiniotis G | |||||||||
Citation | Journal: Nature / Year: 2020 Title: Structure of the neurotensin receptor 1 in complex with β-arrestin 1. Authors: Weijiao Huang / Matthieu Masureel / Qianhui Qu / John Janetzko / Asuka Inoue / Hideaki E Kato / Michael J Robertson / Khanh C Nguyen / Jeffrey S Glenn / Georgios Skiniotis / Brian K Kobilka / Abstract: Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization and affecting various downstream ...Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization and affecting various downstream signalling pathways. Although there is a wealth of structural information detailing the interactions between GPCRs and G proteins, less is known about how arrestins engage GPCRs. Here we report a cryo-electron microscopy structure of full-length human neurotensin receptor 1 (NTSR1) in complex with truncated human β-arrestin 1 (βarr1(ΔCT)). We find that phosphorylation of NTSR1 is critical for the formation of a stable complex with βarr1(ΔCT), and identify phosphorylated sites in both the third intracellular loop and the C terminus that may promote this interaction. In addition, we observe a phosphatidylinositol-4,5-bisphosphate molecule forming a bridge between the membrane side of NTSR1 transmembrane segments 1 and 4 and the C-lobe of arrestin. Compared with a structure of a rhodopsin-arrestin-1 complex, in our structure arrestin is rotated by approximately 85° relative to the receptor. These findings highlight both conserved aspects and plasticity among arrestin-receptor interactions. | |||||||||
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_20836.map.gz | 3.2 MB | EMDB map data format | |
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Header (meta data) | emd-20836-v30.xml emd-20836.xml | 13.2 KB 13.2 KB | Display Display | EMDB header |
Images | emd_20836.png | 43.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20836 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20836 | HTTPS FTP |
-Related structure data
Related structure data | 6up7MC 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_20836.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 : NTSR_Arrestin
Entire | Name: NTSR_Arrestin |
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Components |
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-Supramolecule #1: NTSR_Arrestin
Supramolecule | Name: NTSR_Arrestin / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: ARG-ARG-PRO-TYR-ILE-LEU
Macromolecule | Name: ARG-ARG-PRO-TYR-ILE-LEU / 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: 819.007 Da |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: RRPYIL |
-Macromolecule #2: Beta-arrestin-1
Macromolecule | Name: Beta-arrestin-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: 39.06284 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: VFKKASPNGK LTVYLGKRDF VDHIDLVDPV DGVVLVDPEY LKERRVYVTL TVAFRYGRED LDVLGLTFRK DLFVANVQSF PPAPEDKKP LTRLQERLIK KLGEHAYPFT FEIPPNLPSS VTLQPGPEDT GKALGVDYEV KAFVAENLEE KIHKRNSVRL V IRKVQYAP ...String: VFKKASPNGK LTVYLGKRDF VDHIDLVDPV DGVVLVDPEY LKERRVYVTL TVAFRYGRED LDVLGLTFRK DLFVANVQSF PPAPEDKKP LTRLQERLIK KLGEHAYPFT FEIPPNLPSS VTLQPGPEDT GKALGVDYEV KAFVAENLEE KIHKRNSVRL V IRKVQYAP ERPGPQPTAE TTRQFLMSDK PLHLEASLDK EIYYHGEPIS VNVHVTNNTN KTVKKIKISV RQYADIVLFN TA QYKVPVA MEEADDTVAP SSTFSKVYTL TPFLANNREK RGLALDGKLK HEDTNLASST LLREGANREI LGIIVSYKVK VKL VVSRGG LLGDLASSDV AVELPFTLMH PK |
-Macromolecule #3: Neurotensin receptor type 1
Macromolecule | Name: Neurotensin receptor type 1 / type: protein_or_peptide / ID: 3 Details: missing regions were not modeled due to local low resolution/flexibility. Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.360656 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: PSSELDVNTD IYSKVLVTAV YLALFVVGTV GNTVTAFTLA RKKSLQSLQS TVHYHLGSLA LSDLLTLLLA MPVELYNFIW VHHPWAFGD AGCRGYYFLR DACTYATALN VASLSVERYL AICHPFKAKT LMSRSRTKKF ISAIWLASAL LAVPMLFTMG E QNRSADGQ ...String: PSSELDVNTD IYSKVLVTAV YLALFVVGTV GNTVTAFTLA RKKSLQSLQS TVHYHLGSLA LSDLLTLLLA MPVELYNFIW VHHPWAFGD AGCRGYYFLR DACTYATALN VASLSVERYL AICHPFKAKT LMSRSRTKKF ISAIWLASAL LAVPMLFTMG E QNRSADGQ HAGGLVCTPT IHTATVKVVI QVNTFMSFIF PMVVISVLNT IIANKLTVMV RQAAEQGQVC TVGGEHSTFS MA IEPGRVQ ALRHGVRVLR AVVIAFVVCW LPYHVRRLMF CYISDEQWTP FLYDFYHYFY MVTNALFYVS STINPILYNL VSA NFRHIF LATLACLC |
-Macromolecule #4: unidentified peptide
Macromolecule | Name: unidentified peptide / type: protein_or_peptide / ID: 4 Details: actual sequence for this poly-A exists, however, the local resolution for this region is not sufficient to register the amino acids. Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 783.958 Da |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) |
-Macromolecule #5: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(o...
Macromolecule | Name: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate type: ligand / ID: 5 / Number of copies: 1 / Formula: PIO |
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Molecular weight | Theoretical: 746.566 Da |
Chemical component information | ChemComp-PIO: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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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: OTHER |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 56.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 254725 |