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Yorodumi- EMDB-25821: Lysophosphatidic acid receptor 1-Gi complex bound to LPA, state a -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25821 | ||||||||||||
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Title | Lysophosphatidic acid receptor 1-Gi complex bound to LPA, state a | ||||||||||||
Map data | |||||||||||||
Sample |
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Function / homology | Function and homology information Adenylate cyclase inhibitory pathway / cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / : / Lysosphingolipid and LPA receptors / lysophosphatidic acid binding / Extra-nuclear estrogen signaling ...Adenylate cyclase inhibitory pathway / cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / : / Lysosphingolipid and LPA receptors / lysophosphatidic acid binding / 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 / negative regulation of cilium assembly / regulation of synaptic vesicle cycle / corpus callosum development / oligodendrocyte development / bleb assembly / negative regulation of cAMP-mediated signaling / Activation of the phototransduction cascade / cellular response to oxygen levels / regulation of metabolic process / GTPase activating protein binding / regulation of postsynaptic neurotransmitter receptor internalization / 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 / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / optic nerve development / positive regulation of Rho protein signal transduction / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of dendritic spine development / G-protein alpha-subunit binding / D2 dopamine receptor binding / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / GABA-ergic synapse / regulation of mitotic spindle organization / positive regulation of stress fiber assembly / myelination / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / neurogenesis / G-protein beta/gamma-subunit complex binding / cell chemotaxis / cerebellum development / dendritic shaft / G protein-coupled receptor binding / G protein-coupled receptor activity / PDZ domain binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / GDP binding / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / negative regulation of neuron projection development / presynaptic membrane / regulation of cell shape / cell cortex / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / midbody / G alpha (q) signalling events / positive regulation of canonical NF-kappaB signal transduction / postsynaptic membrane / positive regulation of MAPK cascade / dendritic spine / endosome / positive regulation of apoptotic process / G protein-coupled receptor signaling pathway / cell division / GTPase activity Similarity search - Function | ||||||||||||
Biological species | Bos taurus (cattle) / Homo sapiens (human) / Rattus norvegicus (Norway rat) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.11 Å | ||||||||||||
Authors | Liu S / Paknejad N / Zhu L / Kihara Y / Ray D / Chun J / Liu W / Hite RK / Huang XY | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nat Commun / Year: 2022 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
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_25821.map.gz | 9.2 MB | EMDB map data format | |
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Header (meta data) | emd-25821-v30.xml emd-25821.xml | 14.2 KB 14.2 KB | Display Display | EMDB header |
Images | emd_25821.png | 88.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25821 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25821 | HTTPS FTP |
-Validation report
Summary document | emd_25821_validation.pdf.gz | 364.8 KB | Display | EMDB validaton report |
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Full document | emd_25821_full_validation.pdf.gz | 364.3 KB | Display | |
Data in XML | emd_25821_validation.xml.gz | 4.6 KB | Display | |
Data in CIF | emd_25821_validation.cif.gz | 5.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25821 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25821 | HTTPS FTP |
-Related structure data
Related structure data | 7td2MC 7td0C 7td1C 7td3C 7td4C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_25821.map.gz / Format: CCP4 / Size: 9.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.064 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : complex of Lysophosphatidic Acid Receptor 1 with G-protein and LPA
Entire | Name: complex of Lysophosphatidic Acid Receptor 1 with G-protein and LPA |
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Components |
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-Supramolecule #1: complex of Lysophosphatidic Acid Receptor 1 with G-protein and LPA
Supramolecule | Name: complex of Lysophosphatidic Acid Receptor 1 with G-protein and LPA type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Bos taurus (cattle) |
-Macromolecule #1: Lysophosphatidic acid receptor 1
Macromolecule | Name: Lysophosphatidic acid receptor 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 39.734605 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DYKDDDDKAA AAAISTSIPV ISQPQFTAMN EPQCFYNESI AFFYNRSGKH LATEWNTVSK LVMGLGITVC IFIMLANLLV MVAIYVNRR FHFPIYYLMA NLAAADFFAG LAYFYLMFNT GPNTRRLTVS TWLLRQGLID TSLTASVANL LAIAIERHIT V FRMQLHTR ...String: DYKDDDDKAA AAAISTSIPV ISQPQFTAMN EPQCFYNESI AFFYNRSGKH LATEWNTVSK LVMGLGITVC IFIMLANLLV MVAIYVNRR FHFPIYYLMA NLAAADFFAG LAYFYLMFNT GPNTRRLTVS TWLLRQGLID TSLTASVANL LAIAIERHIT V FRMQLHTR MSNRRVVVVI VVIWTMAIVM GAIPSVGWNC ICDIENCSNM APLYSDSYLV FWAIFNLVTF VVMVVLYAHI FG YVRQRTM RMSRHSSGPR RNRDTMMSLL KTVVIVLGAF IICWTPGLVL LLLDVCCPQC DVLAYEKFFL LLAEFNSAMN PII YSYRDK EMSATFRQIL CCQRSENPTG PTEG |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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 #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 43.16307 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
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 #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 7.845078 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L |
-Macromolecule #5: (2R)-2-hydroxy-3-(phosphonooxy)propyl (9E)-octadec-9-enoate
Macromolecule | Name: (2R)-2-hydroxy-3-(phosphonooxy)propyl (9E)-octadec-9-enoate type: ligand / ID: 5 / Number of copies: 1 / Formula: NKP |
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Molecular weight | Theoretical: 436.52 Da |
Chemical component information | ChemComp-NKP: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 28.2 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.11 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 32504 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |