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Open data
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Basic information
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Title | Structure of beta-arrestin1 in complex with D6Rpp | |||||||||||||||
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![]() | GPCR / Arrestin / SIGNALING PROTEIN / SYGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | ![]() V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / G alpha (s) signalling events / alpha-1B adrenergic receptor binding / follicle-stimulating hormone signaling pathway / protein phosphorylated amino acid binding / angiotensin receptor binding / Lysosome Vesicle Biogenesis ...V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / G alpha (s) signalling events / alpha-1B adrenergic receptor binding / follicle-stimulating hormone signaling pathway / protein phosphorylated amino acid binding / angiotensin receptor binding / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / Golgi Associated Vesicle Biogenesis / chemokine receptor activity / MAP2K and MAPK activation / Ub-specific processing proteases / positive regulation of smooth muscle cell apoptotic process / negative regulation of interleukin-8 production / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / clathrin adaptor activity / scavenger receptor activity / C-C chemokine receptor activity / regulation of G protein-coupled receptor signaling pathway / C-C chemokine binding / arrestin family protein binding / G protein-coupled receptor internalization / response to morphine / Chemokine receptors bind chemokines / Thrombin signalling through proteinase activated receptors (PARs) / mitogen-activated protein kinase kinase binding / clathrin binding / positive regulation of Rho protein signal transduction / stress fiber assembly / negative regulation of Notch signaling pathway / pseudopodium / positive regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of interleukin-6 production / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / positive regulation of receptor internalization / phototransduction / clathrin-coated pit / negative regulation of protein ubiquitination / visual perception / GTPase activator activity / cell chemotaxis / negative regulation of protein phosphorylation / positive regulation of protein ubiquitination / G protein-coupled receptor binding / actin filament / nuclear estrogen receptor binding / calcium-mediated signaling / phosphoprotein binding / insulin-like growth factor receptor binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / recycling endosome / negative regulation of ERK1 and ERK2 cascade / endocytosis / protein transport / positive regulation of peptidyl-serine phosphorylation / positive regulation of cytosolic calcium ion concentration / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / basolateral plasma membrane / postsynaptic membrane / regulation of apoptotic process / nuclear membrane / proteasome-mediated ubiquitin-dependent protein catabolic process / transmembrane transporter binding / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / dendritic spine / transcription coactivator activity / early endosome / positive regulation of ERK1 and ERK2 cascade / protein ubiquitination / intracellular signal transduction / endosome / response to xenobiotic stimulus / inflammatory response / positive regulation of protein phosphorylation / immune response / G protein-coupled receptor signaling pathway / external side of plasma membrane / intracellular membrane-bounded organelle / signaling receptor binding / ubiquitin protein ligase binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / chromatin / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||||||||
![]() | Maharana J / Sarma P / Yadav MK / Chami M / Banerjee R / Shukla AK | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors. Authors: Jagannath Maharana / Fumiya K Sano / Parishmita Sarma / Manish K Yadav / Longhan Duan / Tomasz M Stepniewski / Madhu Chaturvedi / Ashutosh Ranjan / Vinay Singh / Sayantan Saha / Gargi ...Authors: Jagannath Maharana / Fumiya K Sano / Parishmita Sarma / Manish K Yadav / Longhan Duan / Tomasz M Stepniewski / Madhu Chaturvedi / Ashutosh Ranjan / Vinay Singh / Sayantan Saha / Gargi Mahajan / Mohamed Chami / Wataru Shihoya / Jana Selent / Ka Young Chung / Ramanuj Banerjee / Osamu Nureki / Arun K Shukla / ![]() ![]() ![]() ![]() ![]() Abstract: β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor ...β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor activation and phosphorylation. Here, we present seven cryo-electron microscopy structures of βarrs either in the basal state, activated by the muscarinic receptor subtype 2 (M2R) through its third intracellular loop, or activated by the βarr-biased decoy D6 receptor (D6R). Combined with biochemical, cellular, and biophysical experiments, these structural snapshots allow the visualization of atypical engagement of βarrs with 7TMRs and also reveal a structural transition in the carboxyl terminus of βarr2 from a β strand to an α helix upon activation by D6R. Our study provides previously unanticipated molecular insights into the structural and functional diversity encoded in 7TMR-βarr complexes with direct implications for exploring novel therapeutic avenues. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 83.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.7 KB 22.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.4 KB | Display | ![]() |
Images | ![]() | 65.6 KB | ||
Filedesc metadata | ![]() | 7 KB | ||
Others | ![]() ![]() | 84.5 MB 84.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 779.7 KB | Display | ![]() |
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Full document | ![]() | 779.3 KB | Display | |
Data in XML | ![]() | 17.5 KB | Display | |
Data in CIF | ![]() | 22.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8j8zMC ![]() 8go9C ![]() 8j8rC ![]() 8j8vC ![]() 8j97C ![]() 8j9kC ![]() 8ja3C ![]() 8jafC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.4633 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36082_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36082_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : beta-arrestin1 in complex with D6Rpp
Entire | Name: beta-arrestin1 in complex with D6Rpp |
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Components |
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-Supramolecule #1: beta-arrestin1 in complex with D6Rpp
Supramolecule | Name: beta-arrestin1 in complex with D6Rpp / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: beta-arrestin-1
Supramolecule | Name: beta-arrestin-1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: Fab30 Heavy Chain
Supramolecule | Name: Fab30 Heavy Chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #4: Fab30 Light Chain
Supramolecule | Name: Fab30 Light Chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #5: Phosphopeptide derived from the C-terminal tail of ACKR2 (D6R) re...
Supramolecule | Name: Phosphopeptide derived from the C-terminal tail of ACKR2 (D6R) receptor type: complex / ID: 5 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Beta-arrestin-1
Macromolecule | Name: Beta-arrestin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 47.088508 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA FRYGREDLDV LGLTFRKDLF VANVQSFPP APEDKKPLTR LQERLIKKLG EHAYPFTFEI PPNLPCSVTL QPGPEDTGKA CGVDYEVKAF CAENLEEKIH K RNSVRLVI ...String: MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA FRYGREDLDV LGLTFRKDLF VANVQSFPP APEDKKPLTR LQERLIKKLG EHAYPFTFEI PPNLPCSVTL QPGPEDTGKA CGVDYEVKAF CAENLEEKIH K RNSVRLVI RKVQYAPERP GPQPTAETTR QFLMSDKPLH LEASLDKEIY YHGEPISVNV HVTNNTNKTV KKIKISVRQY AD ICLFNTA QYKCPVAMEE ADDTVAPSST FCKVYTLTPF LANNREKRGL ALDGKLKHED TNLASSTLLR EGANREILGI IVS YKVKVK LVVSRGGLLG DLASSDVAVE LPFTLMHPKP KEEPPHREVP ESETPVDTNL IELDTNDDDI VFEDFARQRL KGMK DDKDE EDDGTGSPHL NNR UniProtKB: Beta-arrestin-1 |
-Macromolecule #2: Fab30 Heavy Chain
Macromolecule | Name: Fab30 Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25.512354 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDK THHHHHHHH |
-Macromolecule #3: Fab30 Light Chain
Macromolecule | Name: Fab30 Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.435064 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #4: Atypical chemokine receptor 2
Macromolecule | Name: Atypical chemokine receptor 2 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 2.352668 KDa |
Sequence | String: G(TPO)AQA(SEP)L(SEP)(SEP)C (SEP)E(SEP)(SEP)IL(TPO)A UniProtKB: Atypical chemokine receptor 2 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 Component:
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Number real images: 9698 / Average electron dose: 53.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 46000 |
Sample stage | Cooling holder cryogen: NITROGEN |