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- EMDB-35724: Cryo-EM structure of the PGF2-alpha-bound human PTGFR-Gq complex -
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Open data
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Basic information
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Title | Cryo-EM structure of the PGF2-alpha-bound human PTGFR-Gq complex | |||||||||
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![]() | GPCR / PTGFR / PGF2-alpha / Gq / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() prostaglandin F receptor activity / parturition / Prostanoid ligand receptors / cellular response to prostaglandin D stimulus / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway ...prostaglandin F receptor activity / parturition / Prostanoid ligand receptors / cellular response to prostaglandin D stimulus / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / response to estradiol / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / response to lipopolysaccharide / Extra-nuclear estrogen signaling / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / positive regulation of cell population proliferation / positive regulation of gene expression / protein-containing complex binding / negative regulation of apoptotic process / signal transduction / extracellular exosome / extracellular region / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.67 Å | |||||||||
![]() | Wu C / Xu Y / Xu HE | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Ligand-induced activation and G protein coupling of prostaglandin F receptor. Authors: Canrong Wu / Youwei Xu / Qian He / Dianrong Li / Jia Duan / Changyao Li / Chongzhao You / Han Chen / Weiliang Fan / Yi Jiang / H Eric Xu / ![]() Abstract: Prostaglandin F (PGF), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled ...Prostaglandin F (PGF), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled receptor (GPCR), the PGF receptor (FP), which also is the primary therapeutic target for glaucoma and several other diseases. Here, we report cryo-electron microscopy (cryo-EM) structures of the human FP bound to endogenous ligand PGF and anti-glaucoma drugs LTPA and TFPA at global resolutions of 2.67 Å, 2.78 Å, and 3.14 Å. These structures reveal distinct features of FP within the lipid receptor family in terms of ligand binding selectivity, its receptor activation, and G protein coupling mechanisms, including activation in the absence of canonical PIF and ERY motifs and G coupling through direct interactions with receptor transmembrane helix 1 and intracellular loop 1. Together with mutagenesis and functional studies, our structures reveal mechanisms of ligand recognition, receptor activation, and G protein coupling by FP, which could facilitate rational design of FP-targeting drugs. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 60 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.2 KB 20.2 KB | Display Display | ![]() |
Images | ![]() | 39.6 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
Others | ![]() ![]() | 49.8 MB 49.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8iukMC ![]() 8iulC ![]() 8iumC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 0.824 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_35724_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35724_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Cryo-EM structure of the PGF2-alpha-bound human PTGFR-Gq complex
Entire | Name: Cryo-EM structure of the PGF2-alpha-bound human PTGFR-Gq complex |
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Components |
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-Supramolecule #1: Cryo-EM structure of the PGF2-alpha-bound human PTGFR-Gq complex
Supramolecule | Name: Cryo-EM structure of the PGF2-alpha-bound human PTGFR-Gq complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 160 KDa |
-Macromolecule #1: G subunit alpha (q)
Macromolecule | Name: G subunit alpha (q) / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.724383 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTSGIFETK FQVDKVNFHM FDVGAQRDER RKWIQCFNDV TAIIFVVDSS DYNRLQEALN DF KSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRKEFVDIST ASG DGRHIC YPHFTCSVDT ENARRIFNDC KDIILQMNLR EYNLV |
-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: ![]() |
Molecular weight | Theoretical: 37.771367 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQDG KLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL SCCRFLDDNQ I VTSSGDTT ...String: MLLQSELDQL RQEAEQLKNQ IRDARKACAD ATLSQITNNI DPVGRIQMRT RRTLRGHLAK IYAMHWGTDS RLLVSASQDG KLIIWDSYT TNKVHAIPLR SSWVMTCAYA PSGNYVACGG LDNICSIYNL KTREGNVRVS RELAGHTGYL SCCRFLDDNQ I VTSSGDTT CALWDIETGQ QTTTFTGHTG DVMSLSLAPD TRLFVSGACD ASAKLWDVRE GMCRQTFTGH ESDINAICFF PN GNAFATG SDDATCRLFD LRADQELMTY SHDNIICGIT SVSFSKSGRL LLAGYDDFNC NVWDALKADR AGVLAGHDNR VSC LGVTDD GMAVATGSWD SFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: Antibody fragment scFv16
Macromolecule | Name: Antibody fragment scFv16 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 26.277299 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL |
-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: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #5: nanobody Nb35
Macromolecule | Name: nanobody Nb35 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 16.097194 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS S |
-Macromolecule #6: Prostaglandin F2-alpha receptor
Macromolecule | Name: Prostaglandin F2-alpha receptor / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 40.096488 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSMNNSKQLV SPAAALLSNT TCQTENRLSV FFSVIFMTVG ILSNSLAIAI LMKAYQRFRQ KSKASFLLLA SGLVITDFFG HLINGAIAV FVYASDKEWI RFDQSNVLCS IFGICMVFSG LCPLLLGSVM AIERCIGVTK PIFHSTKITS KHVKMMLSGV C LFAVFIAL ...String: MSMNNSKQLV SPAAALLSNT TCQTENRLSV FFSVIFMTVG ILSNSLAIAI LMKAYQRFRQ KSKASFLLLA SGLVITDFFG HLINGAIAV FVYASDKEWI RFDQSNVLCS IFGICMVFSG LCPLLLGSVM AIERCIGVTK PIFHSTKITS KHVKMMLSGV C LFAVFIAL LPILGHRDYK IQASRTWCFY NTEDIKDWED RFYLLLFSFL GLLALGVSLL CNAITGITLL RVKFKSQQHR QG RSHHLEM VIQLLAIMCV SCICWSPFLV TMANIGINGN HSLETCETTL FALRMATWNQ ILDPWVYILL RKAVLKNLYK LAS QCCGVH VISLHIWELS SIKNSLKVAA ISESPVAEKS AST UniProtKB: Prostaglandin F2-alpha receptor |
-Macromolecule #7: (Z)-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(E,3S)-3-oxidanyloct-1-...
Macromolecule | Name: (Z)-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(E,3S)-3-oxidanyloct-1-enyl]cyclopentyl]hept-5-enoic acid type: ligand / ID: 7 / Number of copies: 1 / Formula: UGU |
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Molecular weight | Theoretical: 354.481 Da |
Chemical component information | ![]() ChemComp-UGU: |
-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: 7.5 |
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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: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.67 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 479164 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |