[English] 日本語
![](img/lk-miru.gif)
- EMDB-38401: Latanoprost acid bound Prostaglandin F2-alpha receptor-Gq Protein... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Latanoprost acid bound Prostaglandin F2-alpha receptor-Gq Protein Complex | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | cryo-EM / Complex / Signaling Protein / 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) / response to estradiol / GTPase binding / 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 / Ras protein signal transduction / G alpha (q) signalling events / Extra-nuclear estrogen signaling / cell population proliferation / response to lipopolysaccharide / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / positive regulation of cell population proliferation / synapse / positive regulation of gene expression / negative regulation of apoptotic process / protein-containing complex binding / signal transduction / extracellular exosome / extracellular region / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.85 Å | |||||||||
![]() | Zhang X / Li X / Liu G / Gong W | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Structural basis for ligand recognition and activation of the prostanoid receptors. Authors: Xiu Li / Xuan Zhang / Xin Wen / Daolai Zhang / Changxiu Qu / Xinyi Miao / Wenkai Zhang / Ru Zhang / Guibing Liu / Peng Xiao / Jin-Peng Sun / Weimin Gong / ![]() Abstract: Prostaglandin F (PGF) and thromboxane A (TXA) are endogenous arachidonic acid metabolites, modulating diverse physiological processes including inflammation and cardiovascular homeostasis through ...Prostaglandin F (PGF) and thromboxane A (TXA) are endogenous arachidonic acid metabolites, modulating diverse physiological processes including inflammation and cardiovascular homeostasis through activating PGF receptor (FP) and TXA receptor (TP). Ligands targeting FP and TP have demonstrated efficacy in treating conditions like glaucoma and cardiovascular diseases in humans, as well as reproductive-related diseases in animals. Here, we present five cryoelectron microscopy structures illustrating FP and TP in complex with G and bound to PGF (endogenous ligand), latanoprost acid (a clinical drug), and two other synthetic agonists. Combined with mutational and functional studies, these structures reveal not only structural features for the specific recognition of endogenous ligands and attainment of receptor selectivity of FP and TP but also the common mechanisms of receptor activation and G protein coupling. The findings may enrich our knowledge of ligand recognition and signal transduction of the prostanoid receptor family and facilitate rational ligand design toward these two receptors. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 18.2 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 19.3 KB 19.3 KB | Display Display | ![]() |
Images | ![]() | 48.2 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
Others | ![]() ![]() | 20.7 MB 20.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8xjmMC ![]() 8xjkC ![]() 8xjlC ![]() 8xjnC ![]() 8xjoC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #1
File | emd_38401_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_38401_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Latanoprost acid-FP-miniGq-scFv16 complex
Entire | Name: Latanoprost acid-FP-miniGq-scFv16 complex |
---|---|
Components |
|
-Supramolecule #1: Latanoprost acid-FP-miniGq-scFv16 complex
Supramolecule | Name: Latanoprost acid-FP-miniGq-scFv16 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Engineered miniGq
Macromolecule | Name: Engineered miniGq / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 28.084832 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...String: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRKEFV DISTASGDGR HICYPHFTCA VDTENARRIF NDCKDIILQM NL REYNLV |
-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 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 40.845559 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWNGSSGGG GSGGGGSSGV SGWRLFKKIS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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 |
---|---|
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 #4: Antibody fragment scFv16
Macromolecule | Name: Antibody fragment scFv16 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 27.259344 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQATSSVPVT PGESVSISCR S SKSLLHSN ...String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG SGGGGSDIVM TQATSSVPVT PGESVSISCR S SKSLLHSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GA GTKLELL EENLYFQ |
-Macromolecule #5: Fusion tag,Prostaglandin F2-alpha receptor,LgBiT
Macromolecule | Name: Fusion tag,Prostaglandin F2-alpha receptor,LgBiT / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 64.767266 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DYKDDDDHHH HHHHHGQPGN GSAFLLAPNG SHAPDHNVTQ QRDEGGSGQP GNGSAFLLAP NGSHAPDHNV TQQRDEENLY FQGVDMSMN NSKQLVSPAA ALLSNTTCQT ENRLSVFFSV IFMTVGILSN SLAIAILMKA YQRFRQKSKA SFLLLASGLV I TDFFGHLI ...String: DYKDDDDHHH HHHHHGQPGN GSAFLLAPNG SHAPDHNVTQ QRDEGGSGQP GNGSAFLLAP NGSHAPDHNV TQQRDEENLY FQGVDMSMN NSKQLVSPAA ALLSNTTCQT ENRLSVFFSV IFMTVGILSN SLAIAILMKA YQRFRQKSKA SFLLLASGLV I TDFFGHLI NGAIAVFVYA SDKEWIRFDQ SNVLCSIFGI CMVFSGLCPL LLGSVMAIER CIGVTKPIFH STKITSKHVK MM LSGVCLF AVFIALLPIL GHRDYKIQAS RTWCFYNTED IKDWEDRFYL LLFSFLGLLA LGVSLLCNAI TGITLLRVKF KSQ QHRQGR SHHLEMVIQL LAIMCVSCIC WSPFLVTMAN IGINGNHSLE TCETTLFALR MATWNQILDP WVYILLRKAV LKNL YKLAS QCCGVHVGSS GGGGSGGGGS SGAAAVFTLE DFVGDWEQTA AYNLDQVLEQ GGVSSLLQNL AVSVTPIQRI VRSGE NALK IDIHVIIPYE GLSADQMAQI EEVFKVVYPV DDHHFKVILP YGTLVIDGVT PNMLNYFGRP YEGIAVFDGK KITVTG TLW NGNKIIDERL ITPDGSMLFR VTINS UniProtKB: Prostaglandin F2-alpha receptor |
-Macromolecule #6: Z-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(3R)-3-oxidanyl-5-phenyl-...
Macromolecule | Name: Z-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(3R)-3-oxidanyl-5-phenyl-pentyl]cyclopentyl]hept-5-enoic acid type: ligand / ID: 6 / Number of copies: 1 / Formula: 7WT |
---|---|
Molecular weight | Theoretical: 390.513 Da |
Chemical component information | ![]() ChemComp-7WT: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
Startup model | Type of model: INSILICO MODEL |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.85 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 91516 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |