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- EMDB-70072: Transmembrane domains of the human sweet receptor (TAS1R2 + TAS1R... -

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Entry
Database: EMDB / ID: EMD-70072
TitleTransmembrane domains of the human sweet receptor (TAS1R2 + TAS1R3) from Class 3 particles (rigidly fitted from PDB:9NOX and 9NOR)
Map data
Sample
  • Complex: Transmembrane domains of the Human sweet receptor (TAS1R2 + TAS1R3)
    • Protein or peptide: Taste receptor type 1 member 3,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: Nanobody 35 (NB35)
    • Protein or peptide: Taste receptor type 1 member 2
KeywordsSweet / taste / receptor / GPCR / TAS1R2 / TAS1R3 / T1R2 / T1R3 / HYDROLASE-IMMUNE SYSTEM complex / human
Function / homology
Function and homology information


sweet taste receptor complex / detection of chemical stimulus involved in sensory perception of sweet taste / sweet taste receptor activity / taste receptor activity / sensory perception of umami taste / sensory perception of sweet taste / Class C/3 (Metabotropic glutamate/pheromone receptors) / positive regulation of cytokinesis / PKA activation in glucagon signalling / hair follicle placode formation ...sweet taste receptor complex / detection of chemical stimulus involved in sensory perception of sweet taste / sweet taste receptor activity / taste receptor activity / sensory perception of umami taste / sensory perception of sweet taste / Class C/3 (Metabotropic glutamate/pheromone receptors) / positive regulation of cytokinesis / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / regulation of insulin secretion / cellular response to glucagon stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor activity / bone development / G-protein beta/gamma-subunit complex binding / platelet aggregation / Olfactory Signaling Pathway / cognition / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / sensory perception of smell / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / G protein activity / GTPase binding / Ca2+ pathway / retina development in camera-type eye / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / receptor complex / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
GPCR, family 3, extracellular calcium-sensing receptor-related / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR ...GPCR, family 3, extracellular calcium-sensing receptor-related / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR / G-protein alpha subunit, group S / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Taste receptor type 1 member 3 / Taste receptor type 1 member 2
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsJuen Z / Lu Z / Yu R / Chang AN / Wang B / Fitzpatrick AWP / Zuker CS
Funding support United States, 1 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Cell / Year: 2025
Title: The structure of human sweetness.
Authors: Zhang Juen / Zhengyuan Lu / Ruihuan Yu / Andrew N Chang / Brian Wang / Anthony W P Fitzpatrick / Charles S Zuker /
Abstract: In humans, the detection and ultimately the perception of sweetness begin in the oral cavity, where taste receptor cells (TRCs) dedicated to sweet-sensing interact with sugars, artificial sweeteners, ...In humans, the detection and ultimately the perception of sweetness begin in the oral cavity, where taste receptor cells (TRCs) dedicated to sweet-sensing interact with sugars, artificial sweeteners, and other sweet-tasting chemicals. Human sweet TRCs express on their cell surface a sweet receptor that initiates the cascade of signaling events responsible for our strong attraction to sweet stimuli. Here, we describe the cryo-electron microscopy (cryo-EM) structure of the human sweet receptor bound to two of the most widely used artificial sweeteners-sucralose and aspartame. Our results reveal the structural basis for sweet detection, provide insights into how a single receptor mediates all our responses to such a wide range of sweet-tasting compounds, and open up unique possibilities for designing a generation of taste modulators informed by the structure of the human receptor.
History
DepositionApr 6, 2025-
Header (metadata) releaseMay 14, 2025-
Map releaseMay 14, 2025-
UpdateMay 21, 2025-
Current statusMay 21, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_70072.png

Downloads & links

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Map

FileDownload / File: emd_70072.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
0.82 Å/pix.
x 440 pix.
= 362.12 Å		0.82 Å/pix.
x 440 pix.
= 362.12 Å		0.82 Å/pix.
x 440 pix.
= 362.12 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.823 Å
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Histogram (log scale)
Contour LevelBy AUTHOR: 0.045
Minimum - Maximum-0.2129645 - 0.509001
Average (Standard dev.)0.00012725257 (±0.00876065)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 362.12 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_70072_half_map_1.map
Projections & Slices
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Half map: #2

Fileemd_70072_half_map_2.map
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Sample components

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Entire : Transmembrane domains of the Human sweet receptor (TAS1R2 + TAS1R3)

EntireName: Transmembrane domains of the Human sweet receptor (TAS1R2 + TAS1R3)
Components
  • Complex: Transmembrane domains of the Human sweet receptor (TAS1R2 + TAS1R3)
    • Protein or peptide: Taste receptor type 1 member 3,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: Nanobody 35 (NB35)
    • Protein or peptide: Taste receptor type 1 member 2

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Supramolecule #1: Transmembrane domains of the Human sweet receptor (TAS1R2 + TAS1R3)

SupramoleculeName: Transmembrane domains of the Human sweet receptor (TAS1R2 + TAS1R3)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Taste receptor type 1 member 3,Guanine nucleotide-binding protein...

MacromoleculeName: Taste receptor type 1 member 3,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
EC number: Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 124.469336 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFADYKD DDDKAAAAPL CLSQQLRMKG DYVLGGLFPL GEAEEAGLRS RTRPSSPVCT RFSSNGLLWA LAMKMAVEE INNKSDLLPG LRLGYDLFDT CSEPVVAMKP SLMFLAKAGS RDIAAYCNYT QYQPRVLAVI GPHSSELAMV T GKFFSFFL ...String:
MKTIIALSYI FCLVFADYKD DDDKAAAAPL CLSQQLRMKG DYVLGGLFPL GEAEEAGLRS RTRPSSPVCT RFSSNGLLWA LAMKMAVEE INNKSDLLPG LRLGYDLFDT CSEPVVAMKP SLMFLAKAGS RDIAAYCNYT QYQPRVLAVI GPHSSELAMV T GKFFSFFL MPQVSYGASM ELLSARETFP SFFRTVPSDR VQLTAAAELL QEFGWNWVAA LGSDDEYGRQ GLSIFSALAA AR GICIAHE GLVPLPRADD SRLGKVQDVL HQVNQSSVQV VLLFASVHAA HALFNYSISS RLSPKVWVAS EAWLTSDLVM GLP GMAQMG TVLGFLQRGA QLHEFPQYVK THLALATDPA FCSALGEREQ GLEEDVVGQR CPQCDCITLQ NVSAGLNHHQ TFSV YAAVY SVAQALHNTL QCNASGCPAQ DPVKPWQLLE NMYNLTFHVG GLPLRFDSSG NVDMEYDLKL WVWQGSVPRL HDVGR FNGS LRTERLKIRW HTSDNQKPVS RCSRQCQEGQ VRRVKGFHSC CYDCVDCEAG SYRQNPDDIA CTFCGQDEWS PERSTR CFR RRSRFLAWGE PAVLLLLLLL SLALGLVLAA LGLFVHHRDS PLVQASGGPL ACFGLVCLGL VCLSVLLFPG QPSPARC LA QQPLSHLPLT GCLSTLFLQA AEIFVESELP LSWADRLSGC LRGPWAWLVV LLAMLVEVAL CTWYLVAFPP EVVTDWHM L PTEALVHCRT RSWVSFGLAH ATNATLAFLC FLGTFLVRSQ PGRYNRARGL TFAMLAYFIT WVSFVPLLAN VQVVLRPAV QMGALLLCVL GILAAFHLPR CYLLMRQPGL NTPEFFLGGG PGDAQGQNDG NTGNQGKHEG GGSGGGSGGG SGGGSGGGSG NSKTEDQRN EEKAQREANK KIEKQLQKDK QVYRATHRLL LLGADNSGKS TIVKQMRILH GGSGGSGGTS GIFETKFQVD K VNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVDSSDYN RLQEALNDFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG KS KIEDYFP EFARYTTPED ATPEPGEDPR VTRAKYFIRD EFLRISTASG DGRHYCYPHF TCAVDTQNVK FVFDAVTDII IKE NLKDCG LF

UniProtKB: Taste receptor type 1 member 3, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

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Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.41693 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String:
MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

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Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.861143 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

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Macromolecule #4: Nanobody 35 (NB35)

MacromoleculeName: Nanobody 35 (NB35) / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 17.352498 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A

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Macromolecule #5: Taste receptor type 1 member 2

MacromoleculeName: Taste receptor type 1 member 2 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 96.239008 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFAYPYD VPDYAAAAEP AENSDFYLPG DYLLGGLFSL HANMKGIVHL NFLQVPMCKE YEVKVIGYNL MQAMRFAVE EINNDSSLLP GVLLGYEIVD VCYISNNVQP VLYFLAHEDN LLPIQEDYSN YISRVVAVIG PDNSESVMTV A NFLSLFLL ...String:
MKTIIALSYI FCLVFAYPYD VPDYAAAAEP AENSDFYLPG DYLLGGLFSL HANMKGIVHL NFLQVPMCKE YEVKVIGYNL MQAMRFAVE EINNDSSLLP GVLLGYEIVD VCYISNNVQP VLYFLAHEDN LLPIQEDYSN YISRVVAVIG PDNSESVMTV A NFLSLFLL PQITYSAISD ELRDKVRFPA LLRTTPSADH HIEAMVQLML HFRWNWIIVL VSSDTYGRDN GQLLGERVAR RD ICIAFQE TLPTLQPNQN MTSEERQRLV TIVDKLQQST ARVVVVFSPD LTLYHFFNEV LRQNFTGAVW IASESWAIDP VLH NLTELR HLGTFLGITI QSVPIPGFSE FREWGPQAGP PPLSRTSQSY TCNQECDNCL NATLSFNTIL RLSGERVVYS VYSA VYAVA HALHSLLGCD KSTCTKRVVY PWQLLEEIWK VNFTLLDHQI FFDPQGDVAL HLEIVQWQWD RSQNPFQSVA SYYPL QRQL KNIQDISWHT INNTIPMSMC SKRCQSGQKK KPVGIHVCCF ECIDCLPGTF LNHTEDEYEC QACPNNEWSY QSETSC FKR QLVFLEWHEA PTIAVALLAA LGFLSTLAIL VIFWRHFQTP IVRSAGGPMC FLMLTLLLVA YMVVPVYVGP PKVSTCL CR QALFPLCFTI CISCIAVRSF QIVCAFKMAS RFPRAYSYWV RYQGPYVSMA FITVLKMVIV VIGMLATGLS PTTRTDPD D PKITIVSCNP NYRNSLLFNT SLDLLLSVVG FSFAYMGKEL PTNYNEAKFI TLSMTFYFTS SVSLCTFMSA YSGVLVTIV DLLVTVLNLL AISLGYFGPK CYMILFYPER NTPAYFNSMI QGYTMRRD

UniProtKB: Taste receptor type 1 member 2

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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

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 59.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 723893
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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