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- EMDB-65510: cryoEM structure of S1P3 in complex with heterotrimeric G protein -

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Basic information

Entry
Database: EMDB / ID: EMD-65510
TitlecryoEM structure of S1P3 in complex with heterotrimeric G protein
Map data
Sample
  • Complex: Ternary complex of s1p3 with G protein heterotrimeric
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
    • 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: Sphingosine 1-phosphate receptor 3
KeywordsG protein-coupled receptor / Bitter taste receptor 14 / Bitter taste receptor 46 / ligand binding / signal transduction / MEMBRANE PROTEIN
Function / homology
Function and homology information


negative regulation of establishment of endothelial barrier / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / anatomical structure morphogenesis / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway ...negative regulation of establishment of endothelial barrier / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / anatomical structure morphogenesis / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / mast cell degranulation / chemokine-mediated signaling pathway / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / integrin binding / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / GDP binding / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / GPER1 signaling / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / G-protein beta-subunit binding / extracellular vesicle / positive regulation of cytosolic calcium ion concentration / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / GTPase binding / G protein activity / midbody / Ca2+ pathway / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / ciliary basal body / Ras protein signal transduction / Extra-nuclear estrogen signaling / inflammatory response / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / positive regulation of cell population proliferation / lipid binding / synapse / GTP binding / protein-containing complex binding / magnesium ion binding / signal transduction / extracellular exosome / membrane / nucleus / plasma membrane / cytosol
Similarity search - Function
EDG-3 sphingosine 1-phosphate receptor / Sphingosine 1-phosphate receptor / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit ...EDG-3 sphingosine 1-phosphate receptor / Sphingosine 1-phosphate receptor / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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 / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / 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(i) subunit alpha-1 / Sphingosine 1-phosphate receptor 3
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsWu B / Zhao Q / Tan Q
Funding support China, 3 items
OrganizationGrant numberCountry
National Science Foundation (NSF, China)2022YFA1302900 China
National Science Foundation (NSF, China)82121005 China
National Science Foundation (NSF, China)XDB37030100 China
CitationJournal: Protein Cell / Year: 2026
Title: Structural basis of allosteric and bitopic ligands binding in sphingosine-1-phosphate receptors 2 and 3.
Authors: Yanhong Wu / Qiuru Chen / Hongyu Wang / Kezhen Liu / Jiaxin Wei / Mu Wang / Kun Chen / Ya Zhu / Shuo Han / Cuiying Yi / Limin Ma / Gisela Schnapp / Alexander Pautsch / Christian Gnamm / ...Authors: Yanhong Wu / Qiuru Chen / Hongyu Wang / Kezhen Liu / Jiaxin Wei / Mu Wang / Kun Chen / Ya Zhu / Shuo Han / Cuiying Yi / Limin Ma / Gisela Schnapp / Alexander Pautsch / Christian Gnamm / Matthias Grauert / Esther Schmidt / Qiuxiang Tan / Beili Wu / Qiang Zhao /
History
DepositionJul 24, 2025-
Header (metadata) releaseJun 3, 2026-
Map releaseJun 3, 2026-
UpdateJun 3, 2026-
Current statusJun 3, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_65510.png

Downloads & links

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Map

FileDownload / File: emd_65510.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.05 Å/pix.
x 256 pix.
= 267.52 Å		1.05 Å/pix.
x 256 pix.
= 267.52 Å		1.05 Å/pix.
x 256 pix.
= 267.52 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.045 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0238
Minimum - Maximum-0.13639854 - 0.2511844
Average (Standard dev.)-0.00001876625 (±0.004076747)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 267.52 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_65510_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_65510_half_map_2.map
Projections & Slices
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Histogram (log scale)

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Sample components

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Entire : Ternary complex of s1p3 with G protein heterotrimeric

EntireName: Ternary complex of s1p3 with G protein heterotrimeric
Components
  • Complex: Ternary complex of s1p3 with G protein heterotrimeric
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
    • 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: Sphingosine 1-phosphate receptor 3

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Supramolecule #1: Ternary complex of s1p3 with G protein heterotrimeric

SupramoleculeName: Ternary complex of s1p3 with G protein heterotrimeric / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 120 kDa/nm

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Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1

MacromoleculeName: Guanine nucleotide-binding protein G(i) subunit alpha-1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.447141 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String:
MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVTAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF

UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1

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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: 38.745359 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MHHHHHHGSL LQSELDELRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT RQGNVRVSRE LAGHTGYLSC C RFLDDNQI ...String:
MHHHHHHGSL LQSELDELRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT RQGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP DGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN

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: 6 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString:
IAQARKLVQQ LKMEANIDRI KVSKAAADLM AYCEAHAKED PLLTPVPASQ NPFR

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

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Macromolecule #4: Sphingosine 1-phosphate receptor 3

MacromoleculeName: Sphingosine 1-phosphate receptor 3 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 47.985574 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MKTIIALSYI FCLVFAMATA LPPRLQPVRG NETLREHYQY VGKLAGRLKE ASEGSTLTTV LFLVICSFIV LENLMVLIAI WKNNKFHNR MYFFIGNLAL CDLLAGIAYK VNILMSGKKT FSLSPTVWFL REGSMFVALG ASTCSLLAIA IERHLTMIKM R PYDANKRH ...String:
MKTIIALSYI FCLVFAMATA LPPRLQPVRG NETLREHYQY VGKLAGRLKE ASEGSTLTTV LFLVICSFIV LENLMVLIAI WKNNKFHNR MYFFIGNLAL CDLLAGIAYK VNILMSGKKT FSLSPTVWFL REGSMFVALG ASTCSLLAIA IERHLTMIKM R PYDANKRH RVFLLIGMCW LIAFTLGALP ILGWNCLHNL PDCSTILPLY SKKYIAFCIS IFTAILVTIV ILYARIYFLV KS SSRKVAN HNNSERSMAL LRTVVIVVSV FIACWSPLFI LFLIDVACRV QACPILFKAQ WFIVLAVLNS AMNPVIYTLA SKE MRRAFF RLVCNCLVRG RGARASPIQP ALDPSRSKSS SSNNSSHSPK VKEDLPHTAP SSCIMDKNAA LQNGIFCNWS HPQF EKGGG SGGGSGGSAW SHPQFEKDYK DDDDK

UniProtKB: Sphingosine 1-phosphate receptor 3

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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

Concentration2.0 mg/mL
BufferpH: 7.5 / Component - Concentration: 2.8 mg/ml / Component - Formula: 150mM / Component - Name: sodium chloride
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 1s.
DetailsThis sample was monodisperse

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Electron microscopy

MicroscopeFEI TECNAI F30
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 2 / Number real images: 5405 / Average exposure time: 2.0 sec. / Average electron dose: 40.0 e/Å2 / Details: Images were collected in movie-mode
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

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Image processing

DetailsThe selected images were 20eV using GIF-Quantum LS Imaging energy filter
Particle selectionNumber selected: 669267
CTF correctionSoftware - Name: Gctf (ver. v1.06) / Type: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6omm

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 669267
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
Final 3D classificationSoftware - Name: RELION (ver. 3.0)

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Atomic model buiding 1

Initial modelPDB ID:

7x9a


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Overall B value: 103.75
Output model

PDB-9w0o:
cryoEM structure of S1P3 in complex with heterotrimeric G protein

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