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- EMDB-60642: Agonist-Cryo-EM structure of the orphan GPR52 beta-arrestin 1 com... -

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Basic information

Entry
Database: EMDB / ID: EMD-60642
TitleAgonist-Cryo-EM structure of the orphan GPR52 beta-arrestin 1 complex bound to ligand c17bound GPCR in complex with arrestin
Map data
Sample
  • Complex: The complex of GPCR with arrestin
    • Protein or peptide: G-protein coupled receptor 52
    • Protein or peptide: Beta-arrestin-1
  • Protein or peptide: scFv30 antibody
  • Ligand: N-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide
KeywordsComplex / membrane protein / GPCR / arrestin / beta-arrestin1 / MEMBRANE PROTEIN/IMMUNE SYSTEM / MEMBRANE PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


angiotensin receptor binding / G protein-coupled photoreceptor activity / cellular response to light stimulus / TGFBR3 regulates TGF-beta signaling / Activation of SMO / negative regulation of interleukin-8 production / G protein-coupled receptor internalization / arrestin family protein binding / Lysosome Vesicle Biogenesis / negative regulation of NF-kappaB transcription factor activity ...angiotensin receptor binding / G protein-coupled photoreceptor activity / cellular response to light stimulus / TGFBR3 regulates TGF-beta signaling / Activation of SMO / negative regulation of interleukin-8 production / G protein-coupled receptor internalization / arrestin family protein binding / Lysosome Vesicle Biogenesis / negative regulation of NF-kappaB transcription factor activity / positive regulation of cardiac muscle hypertrophy / stress fiber assembly / Golgi Associated Vesicle Biogenesis / positive regulation of Rho protein signal transduction / pseudopodium / negative regulation of interleukin-6 production / positive regulation of receptor internalization / negative regulation of Notch signaling pathway / enzyme inhibitor activity / phototransduction / insulin-like growth factor receptor binding / clathrin-coated pit / negative regulation of protein ubiquitination / GTPase activator activity / cytoplasmic vesicle membrane / Activated NOTCH1 Transmits Signal to the Nucleus / locomotory behavior / G protein-coupled receptor binding / Signaling by high-kinase activity BRAF mutants / G protein-coupled receptor activity / MAP2K and MAPK activation / positive regulation of protein phosphorylation / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / endocytic vesicle membrane / Signaling by BRAF and RAF1 fusions / Cargo recognition for clathrin-mediated endocytosis / protein transport / Thrombin signalling through proteinase activated receptors (PARs) / Clathrin-mediated endocytosis / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / G alpha (s) signalling events / molecular adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / transcription coactivator activity / positive regulation of ERK1 and ERK2 cascade / Ub-specific processing proteases / protein ubiquitination / nuclear body / G protein-coupled receptor signaling pathway / response to xenobiotic stimulus / Golgi membrane / lysosomal membrane / ubiquitin protein ligase binding / regulation of transcription by RNA polymerase II / chromatin / signal transduction / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
: / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin (or S-antigen), C-terminal domain ...: / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin-like, C-terminal / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / Immunoglobulin E-set
Similarity search - Domain/homology
Beta-arrestin-1 / G-protein coupled receptor 52
Similarity search - Component
Biological speciesHomo sapiens (human) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.86 Å
AuthorsLin X / Xu F
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Cell Res / Year: 2025
Title: Constitutive arrestin recruitment by orphan GPR52 via an atypical binding mode.
Authors: Xi Lin / Xiaohu Wei / Ning Pu / Ling Wang / Zhibin Zhang / Cuixia Li / Yang Yue / Junlin Liu / Qiwen Tan / Qianqian Sun / Fei Xu /
History
DepositionJun 25, 2024-
Header (metadata) releaseSep 3, 2025-
Map releaseSep 3, 2025-
UpdateSep 3, 2025-
Current statusSep 3, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_60642.map.gz / Format: CCP4 / Size: 55.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 244 pix.
= 203.008 Å
0.83 Å/pix.
x 244 pix.
= 203.008 Å
0.83 Å/pix.
x 244 pix.
= 203.008 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density
Contour LevelBy AUTHOR: 0.124
Minimum - Maximum-0.0017918728 - 1.9469551
Average (Standard dev.)0.0022005795 (±0.033419874)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions244244244
Spacing244244244
CellA=B=C: 203.00801 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_60642_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_60642_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : The complex of GPCR with arrestin

EntireName: The complex of GPCR with arrestin
Components
  • Complex: The complex of GPCR with arrestin
    • Protein or peptide: G-protein coupled receptor 52
    • Protein or peptide: Beta-arrestin-1
  • Protein or peptide: scFv30 antibody
  • Ligand: N-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide

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Supramolecule #1: The complex of GPCR with arrestin

SupramoleculeName: The complex of GPCR with arrestin / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: G-protein coupled receptor 52

MacromoleculeName: G-protein coupled receptor 52 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 42.400555 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MNESRWTEWR ILNMSSGIVN VSERHSCPLG FGHYSVVDVC IFETVVIVLL TFLIIAGNLT VIFVFHCAPL LHHYTTSYFI QTMAYADLF VGVSCLVPTL SLLHYSTGVH ESLTCQVFGY IISVLKSVSM WCLACISVDR YLAITKPLSY NQLVTPCRLR I CIILIWIY ...String:
MNESRWTEWR ILNMSSGIVN VSERHSCPLG FGHYSVVDVC IFETVVIVLL TFLIIAGNLT VIFVFHCAPL LHHYTTSYFI QTMAYADLF VGVSCLVPTL SLLHYSTGVH ESLTCQVFGY IISVLKSVSM WCLACISVDR YLAITKPLSY NQLVTPCRLR I CIILIWIY SCLIFLPSFF GWGKPGYHGD IFEWCATSWL TSAYFTGFIV CLLYAPAAFV VCFTYFHIFK ICRQHTKEIN DR RARFPSH EVDSSRETGH SPDRRYAMVL FRITSVFYML WLPYIIYFLL ESSRVLDNPT LSFLTTWLAI SNSFCNPVIY SLS NSVFRL GLRRLSETMC TSCMARGRPL PETGGGDE(SEP)A (TPO)(TPO)A(SEP)(SEP)(SEP)LAKD TSS

UniProtKB: G-protein coupled receptor 52

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Macromolecule #2: Beta-arrestin-1

MacromoleculeName: Beta-arrestin-1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 44.265883 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: FVQFCNKKTY KYSGLFIPSH HRARIRRAMG SPEFPGRLGD KGTRVFKKAS PNGKLTVYLG KRDFVDHIDL VDPVDGVVLV DPEYLKERR VYVTLTVAFR YGREDLDVLG LTFRKDLFVA NVQSFPPAPE DKKPLTRLQE RLIKKLGEHA YPFTFEIPPN L PSSVTLQP ...String:
FVQFCNKKTY KYSGLFIPSH HRARIRRAMG SPEFPGRLGD KGTRVFKKAS PNGKLTVYLG KRDFVDHIDL VDPVDGVVLV DPEYLKERR VYVTLTVAFR YGREDLDVLG LTFRKDLFVA NVQSFPPAPE DKKPLTRLQE RLIKKLGEHA YPFTFEIPPN L PSSVTLQP GPEDTGKALG VDYEVKAFVA ENLEEKIHKR NSVRLVIRKV QYAPERPGPQ PTAETTRQFL MSDKPLHLEA SL DKEIYYH GEPISVNVHV TNNTNKTVKK IKISVRQYAD IVLFNTAQYK VPVAMEEADD TVAPSSTFSK VYTLTPFLAN NRE KRGLAL DGKLKHEDTN LASSTLLREG ANREILGIIV SYKVKVKLVV SRGGLLGDLA SSDVAVELPF TLMHPKP

UniProtKB: Beta-arrestin-1

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Macromolecule #3: scFv30 antibody

MacromoleculeName: scFv30 antibody / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 28.010102 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MVSAIVLYVL LAAAAHSAFA DVQLVESGGG LVQPGGSLRL SCAASGFNVY SSSIHWVRQA PGKGLEWVAS ISSYYGYTYY ADSVKGRFT ISADTSKNTA YLQMNSLRAE DTAVYYCARS RQFWYSGLDY WGQGTLVTVS SSGGGGSGGG GSGGGGSDIQ M TQSPSSLS ...String:
MVSAIVLYVL LAAAAHSAFA DVQLVESGGG LVQPGGSLRL SCAASGFNVY SSSIHWVRQA PGKGLEWVAS ISSYYGYTYY ADSVKGRFT ISADTSKNTA YLQMNSLRAE DTAVYYCARS RQFWYSGLDY WGQGTLVTVS SSGGGGSGGG GSGGGGSDIQ M TQSPSSLS ASVGDRVTIT CRASQSVSSA VAWYQQKPGK APKLLIYSAS SLYSGVPSRF SGSRSGTDFT LTISSLQPED FA TYYCQQY KYVPVTFGQG TKVEIKAAA

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Macromolecule #4: N-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoro...

MacromoleculeName: N-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide
type: ligand / ID: 4 / Number of copies: 1 / Formula: EN6
Molecular weightTheoretical: 489.51 Da
Chemical component information

ChemComp-EN6:
N-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: OTHER
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.7000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.86 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 218365
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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