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Open data
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Basic information
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Title | Structure of beta-arrestin2 in complex with M2Rpp | |||||||||||||||
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![]() | GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Function / homology | ![]() angiotensin receptor binding / Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / G protein-coupled acetylcholine receptor activity / desensitization of G protein-coupled receptor signaling pathway / cholinergic synapse / regulation of smooth muscle contraction / 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 / desensitization of G protein-coupled receptor signaling pathway / cholinergic synapse / regulation of smooth muscle contraction / 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 / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of receptor internalization / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / 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 / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / protein transport / nervous system development / presynaptic membrane / 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 / neuronal cell body / glutamatergic synapse / synapse / dendrite / signal transduction / membrane / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||
![]() | Maharana J / Sano FK / Shihoya W / Banerjee R / Nureki O / Shukla AK | |||||||||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 86.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.4 KB 22.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.4 KB | Display | ![]() |
Images | ![]() | 94 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
Others | ![]() ![]() | 84.4 MB 84.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8j8rMC ![]() 8go9C ![]() 8j8vC ![]() 8j8zC ![]() 8j97C ![]() 8j9kC ![]() 8ja3C ![]() 8jafC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.1989 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36078_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36078_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : beta-arrestin2 in complex with M2Rpp
Entire | Name: beta-arrestin2 in complex with M2Rpp |
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Components |
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-Supramolecule #1: beta-arrestin2 in complex with M2Rpp
Supramolecule | Name: beta-arrestin2 in complex with M2Rpp / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: beta-arrestin2
Supramolecule | Name: beta-arrestin2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: Fab30
Supramolecule | Name: Fab30 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() ![]() |
-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: ![]() |
-Macromolecule #1: Beta-arrestin-2
Macromolecule | Name: Beta-arrestin-2 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 47.217676 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGEKPGTRVF KKSSPNGKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTV AFRYGREDCD VLGLSFRKDL FIANYQAFP PTPNPPRPPT RLQERLLRKL GQHAHPFFFT IPQNLPSSVT LQPGPEDTGK ALGVDFEIRA FVAKSLEEKS H KRNSVRLV ...String: MGEKPGTRVF KKSSPNGKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTV AFRYGREDCD VLGLSFRKDL FIANYQAFP PTPNPPRPPT RLQERLLRKL GQHAHPFFFT IPQNLPSSVT LQPGPEDTGK ALGVDFEIRA FVAKSLEEKS H KRNSVRLV IRKVQFAPEK PGPQPSAETT RHFLMSDRSL HLEASLDKEL YYHGEPLNVN VHVTNNSTKT VKKIKVSVRQ YA DIVLFST AQYKVPVAQV EQDDQVSPSS TFSKVYTITP FLANNREKRG LALDGKLKHE DTNLASSTIV KEGANKEVLG ILV SYRVKV KLVVSRGGDV SVELPFVLMH PKPHDHIALP RPQSAATHPP TLLPSAVPET DAPVDTNLIE FETNYATDDD IVFE DFARL RLKGLKDEDY DDQFC UniProtKB: Beta-arrestin-2 |
-Macromolecule #2: Fab30 Heavy Chain
Macromolecule | Name: Fab30 Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25.512354 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 #3: Fab30 Light Chain
Macromolecule | Name: Fab30 Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.435064 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 |
-Macromolecule #4: Muscarinic acetylcholine receptor M2
Macromolecule | Name: Muscarinic acetylcholine receptor M2 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 2.362918 KDa |
Sequence | String: EI(TPO)QDEN(TPO)V(SEP) (TPO)SLGH(SEP)KD UniProtKB: Muscarinic acetylcholine receptor M2 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 Component:
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Vitrification | Cryogen name: ETHANE |
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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: 2596 / Average electron dose: 56.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
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 |