+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36124 | |||||||||||||||
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Title | Structure of beta-arrestin1 in complex with C3aRpp | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Keywords | GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | Function and homology information V2 vasopressin receptor binding / complement component C3a receptor activity / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / 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 ...V2 vasopressin receptor binding / complement component C3a receptor activity / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / 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 / AP-2 adaptor complex binding / Golgi Associated Vesicle Biogenesis / MAP2K and MAPK activation / Ub-specific processing proteases / 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 / blood circulation / Thrombin signalling through proteinase activated receptors (PARs) / mitogen-activated protein kinase kinase binding / azurophil granule membrane / positive regulation of Rho protein signal transduction / clathrin binding / positive regulation of macrophage chemotaxis / negative regulation of Notch signaling pathway / stress fiber assembly / 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 / Purinergic signaling in leishmaniasis infection / specific granule membrane / clathrin-coated pit / negative regulation of protein ubiquitination / insulin-like growth factor receptor binding / visual perception / GTPase activator activity / Peptide ligand-binding receptors / negative regulation of protein phosphorylation / positive regulation of protein ubiquitination / Regulation of Complement cascade / G protein-coupled receptor binding / G protein-coupled receptor activity / nuclear estrogen receptor binding / phosphoprotein binding / calcium-mediated signaling / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / negative regulation of ERK1 and ERK2 cascade / endocytosis / positive regulation of angiogenesis / chemotaxis / positive regulation of peptidyl-serine phosphorylation / protein transport / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / basolateral plasma membrane / G alpha (i) signalling events / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / postsynaptic membrane / proteasome-mediated ubiquitin-dependent protein catabolic process / regulation of apoptotic process / transcription coactivator activity / negative regulation of neuron apoptotic process / transmembrane transporter binding / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / endosome / dendritic spine / postsynaptic density / protein ubiquitination / positive regulation of protein phosphorylation / response to xenobiotic stimulus / inflammatory response / G protein-coupled receptor signaling pathway / signaling receptor binding / positive regulation of cell population proliferation / ubiquitin protein ligase binding / glutamatergic synapse / regulation of transcription by RNA polymerase II / Neutrophil degranulation / chromatin / negative regulation of apoptotic process / regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleus Similarity search - Function | |||||||||||||||
Biological species | Rattus norvegicus (Norway rat) / Mus musculus (house mouse) / Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.94 Å | |||||||||||||||
Authors | Maharana J / Sarma P / Yadav MK / Chami M / Banerjee R / 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_36124.map.gz | 56.7 MB | EMDB map data format | |
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Header (meta data) | emd-36124-v30.xml emd-36124.xml | 22.6 KB 22.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36124_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_36124.png | 64 KB | ||
Filedesc metadata | emd-36124.cif.gz | 7 KB | ||
Others | emd_36124_half_map_1.map.gz emd_36124_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36124 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36124 | HTTPS FTP |
-Validation report
Summary document | emd_36124_validation.pdf.gz | 720.3 KB | Display | EMDB validaton report |
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Full document | emd_36124_full_validation.pdf.gz | 719.9 KB | Display | |
Data in XML | emd_36124_validation.xml.gz | 16.1 KB | Display | |
Data in CIF | emd_36124_validation.cif.gz | 21 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36124 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36124 | HTTPS FTP |
-Related structure data
Related structure data | 8ja3MC 8go9C 8j8rC 8j8vC 8j8zC 8j97C 8j9kC 8jafC 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_36124.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.4268 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36124_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36124_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : beta-arrestin1 in complex with C3aRpp
Entire | Name: beta-arrestin1 in complex with C3aRpp |
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Components |
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-Supramolecule #1: beta-arrestin1 in complex with C3aRpp
Supramolecule | Name: beta-arrestin1 in complex with C3aRpp / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: beta-arrestin-1
Supramolecule | Name: beta-arrestin-1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
-Supramolecule #3: Fab30 Heavy Chain
Supramolecule | Name: Fab30 Heavy Chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Supramolecule #4: Fab30 Light Chain
Supramolecule | Name: Fab30 Light Chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Supramolecule #5: Phosphopeptide derived from the C-terminal tail of C3aR receptor ...
Supramolecule | Name: Phosphopeptide derived from the C-terminal tail of C3aR receptor (C3aRpp) type: complex / ID: 5 / Parent: 1 / Macromolecule list: #2 |
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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: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 40.075152 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA FRYGREDLDV LGLTFRKDLF VANVQSFPP APEDKKPLTR LQERLIKKLG EHAYPFTFEI PPNLPCSVTL QPGPEDTGKA CGVDYEVKAF CAENLEEKIH K RNSVRLVI ...String: MGDKGTRVFK KASPNGKLTV YLGKRDFVDH IDLVDPVDGV VLVDPEYLKE RRVYVTLTCA FRYGREDLDV LGLTFRKDLF VANVQSFPP APEDKKPLTR LQERLIKKLG EHAYPFTFEI PPNLPCSVTL QPGPEDTGKA CGVDYEVKAF CAENLEEKIH K RNSVRLVI RKVQYAPERP GPQPTAETTR QFLMSDKPLH LEASLDKEIY YHGEPISVNV HVTNNTNKTV KKIKISVRQY AD ICLFNTA QYKCPVAMEE ADDTVAPSST FCKVYTLTPF LANNREKRGL ALDGKLKHED TNLASSTLLR EGANREILGI IVS YKVKVK LVVSRGGLLG DLASSDVAVE LPFTLMHPKP K UniProtKB: Beta-arrestin-1 |
-Macromolecule #2: C3a anaphylatoxin chemotactic receptor
Macromolecule | Name: C3a anaphylatoxin chemotactic receptor / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 1.484165 KDa |
Sequence | String: (SEP)EEL(TPO)R(SEP)(TPO)HC UniProtKB: C3a anaphylatoxin chemotactic receptor |
-Macromolecule #3: Fab30 heavy chain
Macromolecule | Name: Fab30 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 25.512354 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String: EISEVQLVES GGGLVQPGGS LRLSCAASGF NVYSSSIHWV RQAPGKGLEW VASISSYYGY TYYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARSRQFWYSG LDYWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDK THHHHHHHH |
-Macromolecule #4: Fab30 light chain
Macromolecule | Name: Fab30 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 23.435064 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQYKYVPVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 Component:
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Number real images: 13438 / Average electron dose: 49.4 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 46000 |
Sample stage | Cooling holder cryogen: NITROGEN |