+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30975 | |||||||||
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Title | Serotonin 1E (5-HT1E) receptor-Gi protein complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information adenylate cyclase-inhibiting serotonin receptor signaling pathway / Serotonin receptors / serotonin binding / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding ...adenylate cyclase-inhibiting serotonin receptor signaling pathway / Serotonin receptors / serotonin binding / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / 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 / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / electron transport chain / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / response to peptide hormone / 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 / GDP binding / 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 / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / chemical synaptic transmission / Extra-nuclear estrogen signaling / cell population proliferation / periplasmic space / electron transfer activity / iron ion binding / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / dendrite / heme binding / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Xu P / Huang S / Zhang H / Mao C / Zhou XE / Shen DD / Jiang Y / Zhang Y / Xu HE | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2021 Title: Structural insights into the lipid and ligand regulation of serotonin receptors. Authors: Peiyu Xu / Sijie Huang / Huibing Zhang / Chunyou Mao / X Edward Zhou / Xi Cheng / Icaro A Simon / Dan-Dan Shen / Hsin-Yung Yen / Carol V Robinson / Kasper Harpsøe / Bo Svensson / Jia Guo / ...Authors: Peiyu Xu / Sijie Huang / Huibing Zhang / Chunyou Mao / X Edward Zhou / Xi Cheng / Icaro A Simon / Dan-Dan Shen / Hsin-Yung Yen / Carol V Robinson / Kasper Harpsøe / Bo Svensson / Jia Guo / Hualiang Jiang / David E Gloriam / Karsten Melcher / Yi Jiang / Yan Zhang / H Eric Xu / Abstract: Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter that activates the largest subtype family of G-protein-coupled receptors. Drugs that target 5-HT, 5-HT, 5-HT and other 5-HT ...Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter that activates the largest subtype family of G-protein-coupled receptors. Drugs that target 5-HT, 5-HT, 5-HT and other 5-HT receptors are used to treat numerous disorders. 5-HT receptors have high levels of basal activity and are subject to regulation by lipids, but the structural basis for the lipid regulation and basal activation of these receptors and the pan-agonism of 5-HT remains unclear. Here we report five structures of 5-HT receptor-G-protein complexes: 5-HT in the apo state, bound to 5-HT or bound to the antipsychotic drug aripiprazole; 5-HT bound to 5-HT; and 5-HT in complex with a 5-HT- and 5-HT-selective agonist, BRL-54443. Notably, the phospholipid phosphatidylinositol 4-phosphate is present at the G-protein-5-HT interface, and is able to increase 5-HT-mediated G-protein activity. The receptor transmembrane domain is surrounded by cholesterol molecules-particularly in the case of 5-HT, in which cholesterol molecules are directly involved in shaping the ligand-binding pocket that determines the specificity for aripiprazol. Within the ligand-binding pocket of apo-5-HT are structured water molecules that mimic 5-HT to activate the receptor. Together, our results address a long-standing question of how lipids and water molecules regulate G-protein-coupled receptors, reveal how 5-HT acts as a pan-agonist, and identify the determinants of drug recognition in 5-HT receptors. | |||||||||
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_30975.map.gz | 17.8 MB | EMDB map data format | |
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Header (meta data) | emd-30975-v30.xml emd-30975.xml | 18 KB 18 KB | Display Display | EMDB header |
Images | emd_30975.png | 55.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30975 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30975 | HTTPS FTP |
-Validation report
Summary document | emd_30975_validation.pdf.gz | 371.1 KB | Display | EMDB validaton report |
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Full document | emd_30975_full_validation.pdf.gz | 370.7 KB | Display | |
Data in XML | emd_30975_validation.xml.gz | 5.7 KB | Display | |
Data in CIF | emd_30975_validation.cif.gz | 6.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30975 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30975 | HTTPS FTP |
-Related structure data
Related structure data | 7e33MC 7e2xC 7e2yC 7e2zC 7e32C 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_30975.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.045 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 : Serotonin 1E (5-HT1E) receptor-Gi protein complex
Entire | Name: Serotonin 1E (5-HT1E) receptor-Gi protein complex |
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Components |
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-Supramolecule #1: Serotonin 1E (5-HT1E) receptor-Gi protein complex
Supramolecule | Name: Serotonin 1E (5-HT1E) receptor-Gi protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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-Supramolecule #2: receptor-Gi protein
Supramolecule | Name: receptor-Gi protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2, #4-#5 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Supramolecule #3: scFv16
Supramolecule | Name: scFv16 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.414047 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 37.915496 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWN |
-Macromolecule #3: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 26.466486 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL K |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #5: Soluble cytochrome b562,5-hydroxytryptamine receptor 1E
Macromolecule | Name: Soluble cytochrome b562,5-hydroxytryptamine receptor 1E type: protein_or_peptide / ID: 5 Details: The BRIL (soluble cytochrome b562) protein was used as the expression tag Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 57.528371 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DYKDDDDAKL QTMHHHHHHH HHHADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFD ILVGQIDDAL KLANEGKVKE AQAAAEQLKT TRNAYIQKYL ASENLYFQGG TNITNCTTEA SMAIRPKTIT E KMLICMTL ...String: DYKDDDDAKL QTMHHHHHHH HHHADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFD ILVGQIDDAL KLANEGKVKE AQAAAEQLKT TRNAYIQKYL ASENLYFQGG TNITNCTTEA SMAIRPKTIT E KMLICMTL VVITTLTTLL NLAVIMAIGT TKKLHQPANY LICSLAVTDL LVAVLVMPLS IIYIVMDRWK LGYFLCEVWL SV DMTCCTC SIWHLCVIAL DRYWAITNAI EYARKRTAKR AALMILTVWT ISIFISMPPL FWRSHRRLSP PPSQCTIQHD HVI YTIYST LGAFYIPLTL ILILYYRIYH AAKSLYQKRG SSRHLSNRST DSQNSFASCK LTQTFCVSDF STSDPTTEFE KFHA SIRIP PFDNDLDHPG ERQQISSTRE RKAARILGLI LGAFILSWLP FFIKELIVGL SIYTVSSEVA DFLTWLGYVN SLINP LLYT SFNEDFKLAF KKLIRCREHT |
-Macromolecule #6: 3-(1-methylpiperidin-4-yl)-1H-indol-5-ol
Macromolecule | Name: 3-(1-methylpiperidin-4-yl)-1H-indol-5-ol / type: ligand / ID: 6 / Number of copies: 1 / Formula: HVU |
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Molecular weight | Theoretical: 230.306 Da |
Chemical component information | ChemComp-HVU: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 62.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 49310 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 29000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 1486169 |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 163354 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |