+Open data
-Basic information
Entry | Database: PDB / ID: 8j8z | |||||||||||||||
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Title | Structure of beta-arrestin1 in complex with D6Rpp | |||||||||||||||
Components |
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Keywords | SYGNALING PROTEIN/IMMUNE SYSTEM / GPCR / Arrestin / SIGNALING PROTEIN / SYGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | Function and homology information V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / Activation of SMO / 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 ...V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / Activation of SMO / 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 / AP-2 adaptor complex binding / Lysosome Vesicle Biogenesis / Golgi Associated Vesicle Biogenesis / MAP2K and MAPK activation / Ub-specific processing proteases / chemokine receptor activity / positive regulation of smooth muscle cell apoptotic process / C-C chemokine receptor activity / negative regulation of interleukin-8 production / Cargo recognition for clathrin-mediated endocytosis / C-C chemokine binding / Clathrin-mediated endocytosis / clathrin adaptor activity / scavenger receptor activity / regulation of G protein-coupled receptor signaling pathway / arrestin family protein binding / G protein-coupled receptor internalization / Thrombin signalling through proteinase activated receptors (PARs) / Chemokine receptors bind chemokines / mitogen-activated protein kinase kinase binding / positive regulation of Rho protein signal transduction / clathrin binding / stress fiber assembly / negative regulation of Notch signaling pathway / pseudopodium / positive regulation of insulin secretion involved in cellular response to glucose stimulus / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / negative regulation of interleukin-6 production / positive regulation of receptor internalization / phototransduction / clathrin-coated pit / negative regulation of protein ubiquitination / insulin-like growth factor receptor binding / 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 / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / negative regulation of ERK1 and ERK2 cascade / recycling endosome / endocytosis / protein transport / positive regulation of peptidyl-serine phosphorylation / positive regulation of cytosolic calcium ion concentration / ubiquitin-dependent protein catabolic process / cytoplasmic vesicle / postsynaptic membrane / proteasome-mediated ubiquitin-dependent protein catabolic process / basolateral plasma membrane / regulation of apoptotic process / nuclear membrane / negative regulation of neuron apoptotic process / transmembrane transporter binding / dendritic spine / positive regulation of MAPK cascade / transcription coactivator activity / positive regulation of ERK1 and ERK2 cascade / protein ubiquitination / early endosome / endosome / intracellular signal transduction / immune response / response to xenobiotic stimulus / inflammatory response / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / external side of plasma membrane / signaling receptor binding / intracellular membrane-bounded organelle / ubiquitin protein ligase binding / positive regulation of cell population proliferation / chromatin / regulation of DNA-templated transcription / 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 / cytosol / cytoplasm 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: 3.4 Å | |||||||||||||||
Authors | Maharana, J. / Sarma, P. / Yadav, M.K. / Chami, M. / Banerjee, R. / Shukla, A.K. | |||||||||||||||
Funding support | India, 4items
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Citation | Journal: Science / Year: 2024 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8j8z.cif.gz | 240.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8j8z.ent.gz | 182.8 KB | Display | PDB format |
PDBx/mmJSON format | 8j8z.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j8/8j8z ftp://data.pdbj.org/pub/pdb/validation_reports/j8/8j8z | HTTPS FTP |
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-Related structure data
Related structure data | 36082MC 8go9C 8j8rC 8j8vC 8j97C 8j9kC 8ja3C 8jafC 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: 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) #3: 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) #4: Protein/peptide | Mass: 2352.668 Da / Num. of mol.: 2 / Fragment: C-terminal tail / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: O00590 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
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Molecular weight |
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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 | ||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 46000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 53 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 9698 |
Image scans | Movie frames/image: 40 |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 5300908 | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 369871 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 8GO8 Accession code: 8GO8 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||
Refine LS restraints |
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