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Yorodumi- PDB-8go8: Structure of beta-arrestin1 in complex with a phosphopeptide corr... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8go8 | ||||||
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Title | Structure of beta-arrestin1 in complex with a phosphopeptide corresponding to the human C5a anaphylatoxin chemotactic receptor 1, C5aR1 | ||||||
Components |
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Keywords | SIGNALING PROTEIN/IMMUNE SYSTEM / 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 / sensory perception of chemical stimulus / 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 / complement receptor mediated signaling pathway / regulation of G protein-coupled receptor signaling pathway / arrestin family protein binding / G protein-coupled receptor internalization / positive regulation of neutrophil chemotaxis / response to morphine / Thrombin signalling through proteinase activated receptors (PARs) / mitogen-activated protein kinase kinase binding / positive regulation of Rho protein signal transduction / clathrin binding / positive regulation of macrophage chemotaxis / negative regulation of Notch signaling pathway / stress fiber assembly / 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 / insulin-like growth factor receptor binding / visual perception / neutrophil chemotaxis / GTPase activator activity / Peptide ligand-binding receptors / secretory granule membrane / positive regulation of epithelial cell proliferation / negative regulation of protein phosphorylation / positive regulation of protein ubiquitination / Regulation of Complement cascade / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / nuclear estrogen receptor binding / phosphoprotein 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 / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / basolateral plasma membrane / postsynaptic membrane / proteasome-mediated ubiquitin-dependent protein catabolic process / regulation of apoptotic process / negative regulation of neuron apoptotic process / transmembrane transporter binding / positive regulation of MAPK cascade / dendritic spine / transcription coactivator activity / positive regulation of ERK1 and ERK2 cascade / postsynaptic density / defense response to Gram-positive bacterium / endosome / protein ubiquitination / response to xenobiotic stimulus / inflammatory response / immune response / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway Similarity search - Function | ||||||
Biological species | Rattus norvegicus (Norway rat) Mus musculus (house mouse) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.41 Å | ||||||
Authors | Maharana, J. / Sarma, P. / Yadav, M.K. / Banerjee, R. / Shukla, A.K. | ||||||
Funding support | India, 1items
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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, M.K. / Banerjee, R. / Shukla, A.K. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8go8.cif.gz | 269.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8go8.ent.gz | 214.3 KB | Display | PDB format |
PDBx/mmJSON format | 8go8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/go/8go8 ftp://data.pdbj.org/pub/pdb/validation_reports/go/8go8 | HTTPS FTP |
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-Related structure data
Related structure data | 34173MC 8gocC 8gooC 8gp3C 8i0nC 8i0qC 8i0zC 8i10C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 47088.508 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Arrb1 / Production host: Escherichia coli (E. coli) / References: UniProt: P29066 #2: Protein/peptide | Mass: 2698.340 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P21730 #3: Antibody | Mass: 25512.354 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Escherichia coli (E. coli) #4: Antibody | Mass: 23435.064 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Escherichia coli (E. coli) Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Molecular weight | Value: 0.19 MDa / Experimental value: YES | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/2 | ||||||||||||||||||||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 283.15 K / Details: Blotted for 3 seconds before plunging. |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 165000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 56 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 6212 |
Image scans | Movie frames/image: 40 |
-Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4304237 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 84655 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 4JQI Accession code: 4JQI / Source name: PDB / Type: experimental model |