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- PDB-8j97: Structure of Muscarinic receptor (M2R) in complex with beta-arres... -
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Basic information
Entry | Database: PDB / ID: 8j97 | |||||||||||||||
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Title | Structure of Muscarinic receptor (M2R) in complex with beta-arrestin1 (Local refine, cross-linked) | |||||||||||||||
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![]() | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | ![]() MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / clathrin heavy chain binding / Ub-specific processing proteases ...MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / clathrin heavy chain binding / Ub-specific processing proteases / clathrin coat of coated pit / G protein-coupled acetylcholine receptor activity / desensitization of G protein-coupled receptor signaling pathway / cholinergic synapse / Cargo recognition for clathrin-mediated endocytosis / regulation of smooth muscle contraction / inositol hexakisphosphate binding / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / Clathrin-mediated endocytosis / clathrin-dependent endocytosis / G protein-coupled serotonin receptor activity / arrestin family protein binding / G protein-coupled receptor internalization / acetylcholine receptor binding / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (s) signalling events / regulation of heart contraction / clathrin binding / negative regulation of Notch signaling pathway / small molecule binding / pseudopodium / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of receptor internalization / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / asymmetric synapse / axon terminus / visual perception / presynaptic modulation of chemical synaptic transmission / clathrin-coated endocytic vesicle membrane / G protein-coupled receptor binding / response to virus / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / receptor internalization / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / protein transport / nervous system development / presynaptic membrane / G alpha (i) signalling events / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / chemical synaptic transmission / postsynaptic membrane / positive regulation of ERK1 and ERK2 cascade / molecular adaptor activity / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / neuronal cell body / glutamatergic synapse / synapse / dendrite / signal transduction / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||||||||
![]() | Maharana, J. / Sano, F.K. / Shihoya, W. / Banerjee, R. / Nureki, O. / Shukla, A.K. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 114.8 KB | Display | ![]() |
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PDB format | ![]() | 82.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 36090MC ![]() 8go9C ![]() 8j8rC ![]() 8j8vC ![]() 8j8zC ![]() 8j9kC ![]() 8ja3C ![]() 8jafC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 39656.668 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#2: Antibody | Mass: 12861.245 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#3: Antibody | Mass: 11500.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#4: Protein/peptide | Mass: 1226.853 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / 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: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 17869 |
Image scans | Movie frames/image: 40 |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 5235492 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 63372 / 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 | ||||||||||||||||||||||||
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