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Yorodumi- EMDB-36126: Structure of Muscarinic receptor (M2R) in complex with beta-arres... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36126 | |||||||||||||||
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Title | Structure of Muscarinic receptor (M2R) in complex with beta-arrestin1 (Local Refine, non-cross linked) | |||||||||||||||
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Sample |
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Keywords | GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | Function and homology information 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 | Bos taurus (cattle) / Mus musculus (house mouse) / Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||
Authors | Maharana J / Sano FK / Shihoya W / Banerjee R / Nureki O / Shukla AK | |||||||||||||||
Funding support | India, 4 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36126.map.gz | 229.2 MB | EMDB map data format | |
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Header (meta data) | emd-36126-v30.xml emd-36126.xml | 21.7 KB 21.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36126_fsc.xml | 13.7 KB | Display | FSC data file |
Images | emd_36126.png | 69 KB | ||
Filedesc metadata | emd-36126.cif.gz | 6.7 KB | ||
Others | emd_36126_half_map_1.map.gz emd_36126_half_map_2.map.gz | 254.5 MB 254.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36126 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36126 | HTTPS FTP |
-Validation report
Summary document | emd_36126_validation.pdf.gz | 739.5 KB | Display | EMDB validaton report |
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Full document | emd_36126_full_validation.pdf.gz | 739.1 KB | Display | |
Data in XML | emd_36126_validation.xml.gz | 22.7 KB | Display | |
Data in CIF | emd_36126_validation.cif.gz | 29.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36126 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36126 | HTTPS FTP |
-Related structure data
Related structure data | 8jafMC 8go9C 8j8rC 8j8vC 8j8zC 8j97C 8j9kC 8ja3C 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_36126.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36126_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36126_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Muscarinic receptor (M2R) in complex with beta-arrestin1
Entire | Name: Muscarinic receptor (M2R) in complex with beta-arrestin1 |
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Components |
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-Supramolecule #1: Muscarinic receptor (M2R) in complex with beta-arrestin1
Supramolecule | Name: Muscarinic receptor (M2R) in complex with beta-arrestin1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: beta-arrestin1
Supramolecule | Name: beta-arrestin1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Bos taurus (cattle) |
-Supramolecule #3: Fab30
Supramolecule | Name: Fab30 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Supramolecule #4: Muscarinic receptor M2R
Supramolecule | Name: Muscarinic receptor M2R / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Beta-arrestin-1
Macromolecule | Name: Beta-arrestin-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 40.24727 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: GTRVFKKASP NGKLTVYLGK RDFVDHIDLV EPVDGVVLVD PEYLKERRVY VTLTCAFRYG REDLDVLGLT FRKDLFVANV QSFPPAPED KKPLTRLQER LIKKLGEHAY PFTFEIPPNL PCSVTLQPGP EDTGKACGVD YEVKAFCAEN LEEKIHKRNS V RLVIRKVQ ...String: GTRVFKKASP NGKLTVYLGK RDFVDHIDLV EPVDGVVLVD PEYLKERRVY VTLTCAFRYG REDLDVLGLT FRKDLFVANV QSFPPAPED KKPLTRLQER LIKKLGEHAY PFTFEIPPNL PCSVTLQPGP EDTGKACGVD YEVKAFCAEN LEEKIHKRNS V RLVIRKVQ YAPERPGPQP TAETTRQFLM SDKPLHLEAS LDKEIYYHGE PISVNVHVTN NTNKTVKKIK ISVRQYADIC LF NTAQYKC PVAMEEADDT VAPSSTFCKV YTLTPFLANN REKRGLALDG KLKHEDTNLA SSTLLREGAN REILGIIVSY KVK VKLVVS RGGLLGDLAS SDVAVELPFT LMHPKPKEEP PH UniProtKB: Beta-arrestin-1 |
-Macromolecule #2: Fab30 heavy chain
Macromolecule | Name: Fab30 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 12.861245 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: VQLVESGGGL VQPGGSLRLS CAASGFNVYS SSIHWVRQAP GKGLEWVASI SSYYGYTYYA DSVKGRFTIS ADTSKNTAYL QMNSLRAED TAVYYCARSR QFWYSGLDYW GQGTLVTV |
-Macromolecule #3: Fab30 light chain
Macromolecule | Name: Fab30 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 11.50082 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGTD FTLTISSLQP EDFATYYCQ QYKYVPVTFG QGTKVEI |
-Macromolecule #4: Muscarinic acetylcholine receptor M2
Macromolecule | Name: Muscarinic acetylcholine receptor M2 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 983.637 Da |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: (TPO)V(SEP)(TPO)(SEP)LG UniProtKB: Muscarinic acetylcholine receptor M2 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Number real images: 32158 / Average electron dose: 50.0 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: 1.6 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |