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- EMDB-65508: Cryo-EM structure of S1P2 in complex with heterotrimeric G protein -

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Basic information

Entry
Database: EMDB / ID: EMD-65508
TitleCryo-EM structure of S1P2 in complex with heterotrimeric G protein
Map data
Sample
  • Complex: Ternary complex of s1p2 with G protein heterotrimeric
    • Protein or peptide: Sphingosine 1-phosphate receptor 2
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • 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) subunit alpha-1
KeywordsG protein-coupled receptor / Bitter taste receptor 14 / Bitter taste receptor 46 / ligand binding / signal transduction / MEMBRANE PROTEIN
Function / homology
Function and homology information


positive regulation of establishment of endothelial barrier / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of excitatory postsynaptic potential / filopodium assembly / sphingosine-1-phosphate receptor signaling pathway / G protein-coupled peptide receptor activity / regulation of postsynapse assembly / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex ...positive regulation of establishment of endothelial barrier / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of excitatory postsynaptic potential / filopodium assembly / sphingosine-1-phosphate receptor signaling pathway / G protein-coupled peptide receptor activity / regulation of postsynapse assembly / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / 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 / chemokine-mediated signaling pathway / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / excitatory postsynaptic potential / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / integrin binding / response to peptide hormone / G protein-coupled receptor activity / centriolar satellite / 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 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / GDP binding / 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 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / sensory perception of taste / sperm principal piece / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / presynapse / actin cytoskeleton organization / retina development in camera-type eye / GTPase binding / fibroblast proliferation / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / postsynapse / ciliary basal body / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / positive regulation of cell population proliferation / centrosome
Similarity search - Function
EDG-5 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-5 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
Sphingosine 1-phosphate receptor 2 / 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
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 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: 2025
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_65508.png

Downloads & links

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Map

FileDownload / File: emd_65508.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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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.045 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.013
Minimum - Maximum-0.059170574 - 0.11243815
Average (Standard dev.)0.00022904303 (±0.002379179)
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: #1

Fileemd_65508_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_65508_half_map_2.map
Projections & Slices
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Histogram

Histogram (log scale)

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Sample components

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Entire : Ternary complex of s1p2 with G protein heterotrimeric

EntireName: Ternary complex of s1p2 with G protein heterotrimeric
Components
  • Complex: Ternary complex of s1p2 with G protein heterotrimeric
    • Protein or peptide: Sphingosine 1-phosphate receptor 2
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • 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) subunit alpha-1

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Supramolecule #1: Ternary complex of s1p2 with G protein heterotrimeric

SupramoleculeName: Ternary complex of s1p2 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: Sphingosine 1-phosphate receptor 2

MacromoleculeName: Sphingosine 1-phosphate receptor 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 44.592129 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MKTIIALSYI FCLVFAMGSL YSEYLNPNKV QEHYNYTKET LETQETTSRQ VASAFIVILC CAIVVENLLV LIAVARNSKF HSAMYLFLG NLAASDLLAG VAFVANTLLS GSVTLRLTPV QWFAREGSAF ITLSASVFSL LAIAIERHVA IAKVKLYGSD K SCRMLLLI ...String:
MKTIIALSYI FCLVFAMGSL YSEYLNPNKV QEHYNYTKET LETQETTSRQ VASAFIVILC CAIVVENLLV LIAVARNSKF HSAMYLFLG NLAASDLLAG VAFVANTLLS GSVTLRLTPV QWFAREGSAF ITLSASVFSL LAIAIERHVA IAKVKLYGSD K SCRMLLLI GASWLISLVL GGLPILGWNC LGHLEACSTV LPLYAKHYVL CVVTIFSIIL LAIVALYVRI YCVVRSSHAD MA APQTLAL LKTVTIVLGV FIVCWLPAFS ILLLDYACPV HSCPILYKAH YFFAVSTLNS LLNPVIYTWR SRDLRREVLR PLQ CWRPGV GVQGRRRGGT PGHHLLPLRS SSSLERGMHM PTSPTFLEGN TVVWSHPQFE KGGGSGGGSG GSAWSHPQFE KDYK DDDDK

UniProtKB: Sphingosine 1-phosphate receptor 2

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Macromolecule #2: 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: 2 / 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 #3: 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: 3 / 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 #4: Guanine nucleotide-binding protein G(i) subunit alpha-1

MacromoleculeName: Guanine nucleotide-binding protein G(i) subunit alpha-1
type: protein_or_peptide / ID: 4 / 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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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: 11178 / 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: 3399613
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: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 415313
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: 107
Output model

PDB-9w0m:
Cryo-EM structure of S1P2 in complex with heterotrimeric G protein

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