+Open data
-Basic information
Entry | Database: PDB / ID: 8j8r | |||||||||||||||
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Title | Structure of beta-arrestin2 in complex with M2Rpp | |||||||||||||||
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 angiotensin receptor binding / Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / regulation of smooth muscle contraction / desensitization of G protein-coupled receptor signaling pathway / cholinergic synapse / inositol hexakisphosphate binding / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway ...angiotensin receptor binding / Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / regulation of smooth muscle contraction / desensitization of G protein-coupled receptor signaling pathway / cholinergic synapse / inositol hexakisphosphate binding / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled serotonin receptor activity / arrestin family protein binding / G protein-coupled receptor internalization / regulation of heart contraction / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of receptor internalization / endocytic vesicle / asymmetric synapse / axon terminus / clathrin-coated pit / presynaptic modulation of chemical synaptic transmission / phosphatidylinositol binding / clathrin-coated endocytic vesicle membrane / response to virus / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / receptor internalization / protein transport / Cargo recognition for clathrin-mediated endocytosis / presynaptic membrane / Clathrin-mediated endocytosis / nervous system development / G alpha (i) signalling events / chemical synaptic transmission / postsynaptic membrane / positive regulation of ERK1 and ERK2 cascade / molecular adaptor activity / G protein-coupled receptor signaling pathway / dendrite / neuronal cell body / glutamatergic synapse / synapse / signal transduction / membrane / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Bos taurus (cattle) Mus musculus (house mouse) Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||
Authors | Maharana, J. / Sano, F.K. / Shihoya, W. / Banerjee, R. / Nureki, O. / 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 | 8j8r.cif.gz | 351 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8j8r.ent.gz | 277.7 KB | Display | PDB format |
PDBx/mmJSON format | 8j8r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j8/8j8r ftp://data.pdbj.org/pub/pdb/validation_reports/j8/8j8r | HTTPS FTP |
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-Related structure data
Related structure data | 36078MC 8go9C 8j8vC 8j8zC 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: 47217.676 Da / Num. of mol.: 3 Mutation: C17G,C60V,L69V,C126S,C141L,C151V,C243V,C252V,C270S,L278F,S280A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: ARRB2 / Production host: Escherichia coli (E. coli) / References: UniProt: P32120 #2: Antibody | Mass: 25512.354 Da / Num. of mol.: 3 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.: 3 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: 2362.918 Da / Num. of mol.: 3 / Fragment: ICL3 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P08172 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 | Experimental value: NO | ||||||||||||||||||||||||||||||
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
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 FIELDBright-field microscopy / Nominal defocus max: 1600 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm |
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 K3 (6k x 4k) / Num. of real images: 2596 |
Image scans | Movie frames/image: 40 |
-Processing
Software |
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1861553 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 224494 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 8GOC Accession code: 8GOC / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 69.42 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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