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- EMDB-35106: Structure of beta-arrestin1 in complex with a phosphopeptide corr... -
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Open data
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Basic information
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Title | Structure of beta-arrestin1 in complex with a phosphopeptide corresponding to the human C-X-C chemokine receptor type 4, CXCR4 (Local refine) | |||||||||
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![]() | GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / C-X-C motif chemokine 12 receptor activity / G alpha (s) signalling events / regulation of viral process / alpha-1B adrenergic receptor binding / positive regulation of vascular wound healing / follicle-stimulating hormone signaling pathway ...V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / C-X-C motif chemokine 12 receptor activity / G alpha (s) signalling events / regulation of viral process / alpha-1B adrenergic receptor binding / positive regulation of vascular wound healing / follicle-stimulating hormone signaling pathway / protein phosphorylated amino acid binding / positive regulation of macrophage migration inhibitory factor signaling pathway / angiotensin receptor binding / positive regulation of mesenchymal stem cell migration / neuron recognition / response to ultrasound / response to tacrolimus / telencephalon cell migration / C-X-C chemokine receptor activity / Specification of primordial germ cells / CXCL12-activated CXCR4 signaling pathway / Lysosome Vesicle Biogenesis / myosin light chain binding / AP-2 adaptor complex binding / Golgi Associated Vesicle Biogenesis / MAP2K and MAPK activation / Ub-specific processing proteases / myelin maintenance / positive regulation of vasculature development / regulation of programmed cell death / positive regulation of smooth muscle cell apoptotic process / endothelial tube morphogenesis / endothelial cell differentiation / negative regulation of interleukin-8 production / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / clathrin adaptor activity / Signaling by ROBO receptors / regulation of chemotaxis / : / positive regulation of dendrite extension / Formation of definitive endoderm / positive regulation of chemotaxis / 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) / anchoring junction / dendritic cell chemotaxis / mitogen-activated protein kinase kinase binding / clathrin binding / positive regulation of oligodendrocyte differentiation / positive regulation of Rho protein signal transduction / stress fiber assembly / negative regulation of Notch signaling pathway / cell leading edge / epithelial cell development / pseudopodium / cellular response to cytokine stimulus / positive regulation of insulin secretion involved in cellular response to glucose stimulus / detection of temperature stimulus involved in sensory perception of pain / regulation of calcium ion transport / negative regulation of interleukin-6 production / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / positive regulation of receptor internalization / phototransduction / small molecule binding / Binding and entry of HIV virion / regulation of cell adhesion / coreceptor activity / detection of mechanical stimulus involved in sensory perception of pain / cardiac muscle contraction / clathrin-coated pit / negative regulation of protein ubiquitination / visual perception / GTPase activator activity / neurogenesis / cell chemotaxis / negative regulation of protein phosphorylation / ubiquitin binding / response to activity / positive regulation of protein ubiquitination / G protein-coupled receptor binding / G protein-coupled receptor activity / nuclear estrogen receptor binding / calcium-mediated signaling / phosphoprotein binding / insulin-like growth factor receptor binding / neuron migration / response to virus / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / brain development / negative regulation of ERK1 and ERK2 cascade / endocytosis / protein transport / cellular response to xenobiotic stimulus Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.45 Å | |||||||||
![]() | Maharana J / Sarma P / Yadav MK / Banerjee R / Shukla AK | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural snapshots uncover a key phosphorylation motif in GPCRs driving β-arrestin activation. Authors: Jagannath Maharana / Parishmita Sarma / Manish K Yadav / Sayantan Saha / Vinay Singh / Shirsha Saha / Mohamed Chami / Ramanuj Banerjee / Arun K Shukla / ![]() ![]() Abstract: Agonist-induced GPCR phosphorylation is a key determinant for the binding and activation of β-arrestins (βarrs). However, it is not entirely clear how different GPCRs harboring divergent ...Agonist-induced GPCR phosphorylation is a key determinant for the binding and activation of β-arrestins (βarrs). However, it is not entirely clear how different GPCRs harboring divergent phosphorylation patterns impart converging active conformation on βarrs leading to broadly conserved functional responses such as desensitization, endocytosis, and signaling. Here, we present multiple cryo-EM structures of activated βarrs in complex with distinct phosphorylation patterns derived from the carboxyl terminus of different GPCRs. These structures help identify a P-X-P-P type phosphorylation motif in GPCRs that interacts with a spatially organized K-K-R-R-K-K sequence in the N-domain of βarrs. Sequence analysis of the human GPCRome reveals the presence of this phosphorylation pattern in a large number of receptors, and its contribution in βarr activation is demonstrated by targeted mutagenesis experiments combined with an intrabody-based conformational sensor. Taken together, our findings provide important structural insights into the ability of distinct GPCRs to activate βarrs through a significantly conserved mechanism. #1: ![]() Title: Structure of beta-arrestin in complex with a phosphopeptide Authors: Maharana J / Sarma P / Yadav MK / Banerjee R / Shukla AK | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.5 KB 22.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.4 KB | Display | ![]() |
Images | ![]() | 31.9 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
Others | ![]() ![]() | 59.2 MB 59.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 844.1 KB | Display | ![]() |
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Full document | ![]() | 843.6 KB | Display | |
Data in XML | ![]() | 16 KB | Display | |
Data in CIF | ![]() | 20.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8i0qMC ![]() 8go8C ![]() 8gocC ![]() 8gooC ![]() 8gp3C ![]() 8i0nC ![]() 8i0zC ![]() 8i10C 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: 1.6463 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_35106_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35106_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Peptide5 bound beta-arrestin1 in complex with Fab30 - Local refine
Entire | Name: Peptide5 bound beta-arrestin1 in complex with Fab30 - Local refine |
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Components |
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-Supramolecule #1: Peptide5 bound beta-arrestin1 in complex with Fab30 - Local refine
Supramolecule | Name: Peptide5 bound beta-arrestin1 in complex with Fab30 - Local refine type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 190 KDa |
-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: CXC chemokine receptor type 4 phosphopeptide
Supramolecule | Name: CXC chemokine receptor type 4 phosphopeptide / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4 / Details: Chemically synthesized |
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Source (natural) | Organism: ![]() |
-Supramolecule #4: Fab30
Supramolecule | Name: Fab30 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #2-#3 |
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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: C-X-C chemokine receptor type 4
Macromolecule | Name: C-X-C chemokine receptor type 4 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 2.38053 KDa |
Sequence | String: GHSSV(SEP)(TPO)E(SEP)E (SEP)(SEP)(SEP)FH(SEP)(SEP) UniProtKB: C-X-C chemokine receptor type 4 |
-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 / Chamber humidity: 90 % / Chamber temperature: 283.15 K / Instrument: LEICA EM GP / Details: Blotted for 3 seconds before plunging.. |
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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: 5637 / Average electron dose: 49.3 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 |
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Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
Output model | ![]() PDB-8i0q: |