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Yorodumi- EMDB-34173: Structure of beta-arrestin1 in complex with a phosphopeptide corr... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34173 | |||||||||
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Title | Structure of beta-arrestin1 in complex with a phosphopeptide corresponding to the human C5a anaphylatoxin chemotactic receptor 1, C5aR1 | |||||||||
Map data | Full map with pixel size 1.5375 | |||||||||
Sample |
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Keywords | GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / complement component C5a signaling pathway / sensory perception of touch / presynapse organization / regulation of tau-protein kinase activity / G alpha (s) signalling events / alpha-1B adrenergic receptor binding / complement component C5a receptor activity ...V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / complement component C5a signaling pathway / sensory perception of touch / presynapse organization / regulation of tau-protein kinase activity / G alpha (s) signalling events / alpha-1B adrenergic receptor binding / complement component C5a receptor activity / follicle-stimulating hormone signaling pathway / protein phosphorylated amino acid binding / angiotensin receptor binding / Lysosome Vesicle Biogenesis / response to peptidoglycan / AP-2 adaptor complex binding / Golgi Associated Vesicle Biogenesis / MAP2K and MAPK activation / Ub-specific processing proteases / positive regulation of smooth muscle cell apoptotic process / sensory perception of chemical stimulus / negative regulation of interleukin-8 production / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / clathrin adaptor activity / complement receptor mediated signaling pathway / regulation of G protein-coupled receptor signaling pathway / arrestin family protein binding / G protein-coupled receptor internalization / response to morphine / positive regulation of neutrophil chemotaxis / Thrombin signalling through proteinase activated receptors (PARs) / mitogen-activated protein kinase kinase binding / clathrin binding / positive regulation of Rho protein signal transduction / positive regulation of macrophage chemotaxis / stress fiber assembly / negative regulation of Notch signaling pathway / amyloid-beta clearance / 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 / : / positive regulation of vascular endothelial growth factor production / cellular defense response / clathrin-coated pit / negative regulation of protein ubiquitination / visual perception / Peptide ligand-binding receptors / neutrophil chemotaxis / GTPase activator activity / secretory granule membrane / negative regulation of protein phosphorylation / positive regulation of protein ubiquitination / Regulation of Complement cascade / positive regulation of epithelial cell proliferation / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / nuclear estrogen receptor binding / phosphoprotein binding / insulin-like growth factor receptor binding / microglial cell activation / mRNA transcription by RNA polymerase II / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / negative regulation of ERK1 and ERK2 cascade / cognition / endocytosis / positive regulation of angiogenesis / chemotaxis / protein transport / apical part of cell / positive regulation of peptidyl-serine phosphorylation / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / basolateral plasma membrane / postsynaptic membrane / regulation of apoptotic process / 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 / positive regulation of ERK1 and ERK2 cascade / defense response to Gram-positive bacterium / protein ubiquitination / endosome / response to xenobiotic stimulus / inflammatory response / positive regulation of protein phosphorylation / immune response / G protein-coupled receptor signaling pathway / signaling receptor binding Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) / Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.41 Å | |||||||||
Authors | Maharana J / Sarma P / Yadav MK / Banerjee R / Shukla AK | |||||||||
Funding support | India, 1 items
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Citation | Journal: Mol Cell / Year: 2023 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: Journal: Mol.Cell / Year: 2023 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 | emd_34173.map.gz | 59.4 MB | EMDB map data format | |
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Header (meta data) | emd-34173-v30.xml emd-34173.xml | 23.1 KB 23.1 KB | Display Display | EMDB header |
Images | emd_34173.png | 49.4 KB | ||
Filedesc metadata | emd-34173.cif.gz | 6.8 KB | ||
Others | emd_34173_half_map_1.map.gz emd_34173_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34173 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34173 | HTTPS FTP |
-Validation report
Summary document | emd_34173_validation.pdf.gz | 799.8 KB | Display | EMDB validaton report |
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Full document | emd_34173_full_validation.pdf.gz | 799.4 KB | Display | |
Data in XML | emd_34173_validation.xml.gz | 12.2 KB | Display | |
Data in CIF | emd_34173_validation.cif.gz | 14.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34173 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34173 | HTTPS FTP |
-Related structure data
Related structure data | 8go8MC 8gocC 8gooC 8gp3C 8i0nC 8i0qC 8i0zC 8i10C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_34173.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Full map with pixel size 1.5375 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.5375 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half map B with pixel size 1.5375
File | emd_34173_half_map_1.map | ||||||||||||
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Annotation | Half map B with pixel size 1.5375 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A with pixel size 1.5375
File | emd_34173_half_map_2.map | ||||||||||||
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Annotation | Half map A with pixel size 1.5375 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Peptide bound beta-arrestin1 in complex with Fab30
Entire | Name: Peptide bound beta-arrestin1 in complex with Fab30 |
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Components |
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-Supramolecule #1: Peptide bound beta-arrestin1 in complex with Fab30
Supramolecule | Name: Peptide bound beta-arrestin1 in complex with Fab30 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 190 KDa |
-Supramolecule #2: beta-arrestin1
Supramolecule | Name: beta-arrestin1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
-Supramolecule #3: C5a anaphylatoxin chemotactic receptor 1
Supramolecule | Name: C5a anaphylatoxin chemotactic receptor 1 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) / Synthetically produced: Yes |
-Supramolecule #4: Fab30
Supramolecule | Name: Fab30 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-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: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 47.088508 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
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: C5a anaphylatoxin chemotactic receptor 1
Macromolecule | Name: C5a anaphylatoxin chemotactic receptor 1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 2.69834 KDa |
Sequence | String: E(SEP)K(SEP)F(TPO)R(SEP)(TPO)V D(TPO)MAQKTQAV UniProtKB: C5a anaphylatoxin chemotactic receptor 1 |
-Macromolecule #3: Fab30 heavy chain
Macromolecule | Name: Fab30 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 25.512354 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
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 #4: Fab30 light chain
Macromolecule | Name: Fab30 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.435064 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
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 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 283.15 K / Instrument: LEICA EM GP / Details: Blotted for 3 seconds before plunging.. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 6212 / Average electron dose: 56.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
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: 165000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+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-8go8: |