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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-25822 | ||||||||||||
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Title | Sphingosine-1-phosphate receptor 1-Gi complex bound to S1P | ||||||||||||
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Function / homology | ![]() Adenylate cyclase inhibitory pathway / cardiac muscle tissue growth involved in heart morphogenesis / Adrenaline,noradrenaline inhibits insulin secretion / sphingosine-1-phosphate receptor activity / ADP signalling through P2Y purinoceptor 12 / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / T cell migration / Extra-nuclear estrogen signaling ...Adenylate cyclase inhibitory pathway / cardiac muscle tissue growth involved in heart morphogenesis / Adrenaline,noradrenaline inhibits insulin secretion / sphingosine-1-phosphate receptor activity / ADP signalling through P2Y purinoceptor 12 / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / T cell migration / Extra-nuclear estrogen signaling / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (i) signalling events / endothelial cell differentiation / heart trabecula morphogenesis / Activation of the phototransduction cascade / regulation of bone mineralization / regulation of metabolic process / sphingosine-1-phosphate receptor signaling pathway / leukocyte chemotaxis / GTPase activating protein binding / regulation of bone resorption / negative regulation of synaptic transmission / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / positive regulation of positive chemotaxis / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / negative regulation of stress fiber assembly / G alpha (q) signalling events / lamellipodium assembly / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / transmission of nerve impulse / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / regulation of cell adhesion / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G protein-coupled receptor binding / G protein-coupled receptor activity / positive regulation of smooth muscle cell proliferation / cell cycle / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / brain development / adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuron differentiation / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GDP binding / chemotaxis / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / cell migration / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / actin cytoskeleton organization / Interleukin-4 and Interleukin-13 signaling / angiogenesis / cell population proliferation / Potential therapeutics for SARS / cell adhesion / endosome / positive regulation of cell migration / G protein-coupled receptor signaling pathway / membrane raft / cell division / external side of plasma membrane / intracellular membrane-bounded organelle / GTPase activity / centrosome / nucleolus / GTP binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | ||||||||||||
![]() | Liu S / Paknejad N / Zhu L / Kihara Y / Ray D / Chun J / Liu W / Hite RK / Huang XY | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate. Authors: Shian Liu / Navid Paknejad / Lan Zhu / Yasuyuki Kihara / Manisha Ray / Jerold Chun / Wei Liu / Richard K Hite / Xin-Yun Huang / ![]() Abstract: Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). ...Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR-G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P) and heterotrimeric G complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA) and G complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P-targeting drugs. | ||||||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 9.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.6 KB 14.6 KB | Display Display | ![]() |
Images | ![]() | 81.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7td3MC ![]() 7td0C ![]() 7td1C ![]() 7td2C ![]() 7td4C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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: 1.083 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : complex of Sphingosine-1-phosphate receptor 1 with G-protein and S1P
Entire | Name: complex of Sphingosine-1-phosphate receptor 1 with G-protein and S1P |
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Components |
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-Supramolecule #1: complex of Sphingosine-1-phosphate receptor 1 with G-protein and S1P
Supramolecule | Name: complex of Sphingosine-1-phosphate receptor 1 with G-protein and S1P type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: 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 |
-Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 43.16307 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSSHHHHHH SSGLEVLFQG PHMASMGCTL SAEDKAAVER SKMIDRNLRE DGEKAAREVK LLLLGAGESG KSTIVKQMKI IHEAGYSEE ECKQYKAVVY SNTIQSIIAI IRAMGRLKID FGDSARADDA RQLFVLAGAA EEGFMTAELA GVIKRLWKDS G VQACFNRS ...String: MGSSHHHHHH SSGLEVLFQG PHMASMGCTL SAEDKAAVER SKMIDRNLRE DGEKAAREVK LLLLGAGESG KSTIVKQMKI IHEAGYSEE ECKQYKAVVY SNTIQSIIAI IRAMGRLKID FGDSARADDA RQLFVLAGAA EEGFMTAELA GVIKRLWKDS G VQACFNRS REYQLNDSAA YYLNDLDRIA QPNYIPTQQD VLRTRVKTTG IVETHFTFKD LHFKMFDVGA QRSERKKWIH CF EGVTAII FCVALSDYDL VLAEDEEMNR MHESMKLFDS ICNNKWFTDT SIILFLNKKD LFEEKIKKSP LTICYPEYAG SNT YEEAAA YIQCQFEDLN KRKDTKEIYT HFTCATDTKN VQFVFDAVTD VIIKNNLKDC GLF |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: 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 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 7.845078 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L |
-Macromolecule #4: Sphingosine 1-phosphate receptor 1
Macromolecule | Name: Sphingosine 1-phosphate receptor 1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 43.938734 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DYKDDDDKAA AGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII LENIFVLLTI WKTKKFHRP MYYFIGNLAL SDLLAGVAYT ANLLLSGATT YKLTPAQWFL REGSMFVALS ASVFSLLAIA IERYITMLKM K LHNGSNNF ...String: DYKDDDDKAA AGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII LENIFVLLTI WKTKKFHRP MYYFIGNLAL SDLLAGVAYT ANLLLSGATT YKLTPAQWFL REGSMFVALS ASVFSLLAIA IERYITMLKM K LHNGSNNF RLFLLISACW VISLILGGLP IMGWNCISAL SSCSTVLPLY HKHYILFCTT VFTLLLLSIV ILYCRIYSLV RT RSRRLTF RKNISKASRS SEKSLALLKT VIIVLSVFIA CWAPLFILLL LDVGCKVKTC DILFRAEYFL VLAVLNSGTN PII YTLTNK EMRRAFIRIM SCCKCPSGDS AGKFKRPIIA GMEFSRSKSD NSSHPQKDEG DNPETIMSSG NVNSSS |
-Macromolecule #5: (2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate
Macromolecule | Name: (2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate type: ligand / ID: 5 / Number of copies: 1 / Formula: S1P |
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Molecular weight | Theoretical: 379.472 Da |
Chemical component information | ![]() ChemComp-S1P: |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-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 |
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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) / Average electron dose: 24.65 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 449331 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |