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Open data
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Basic information
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Title | Serotonin 4 (5-HT4) receptor-Gi-scFv16 complex | |||||||||
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![]() | GPCR / serotonin receptor / 5-HT / 5-HT4 receptor / signaling complex / cryo-EM structure / ligand selectivity / G protein selectivity / structure-function relationships / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() serotonin receptor activity / large intestinal transit / regulation of appetite / maintenance of gastrointestinal epithelium / mucus secretion / Serotonin receptors / 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 ...serotonin receptor activity / large intestinal transit / regulation of appetite / maintenance of gastrointestinal epithelium / mucus secretion / Serotonin receptors / 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 / adenylate cyclase-activating adrenergic receptor signaling pathway / 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 / 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 activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / response to peptide hormone / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / endosome / iron ion binding / cell cycle / 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 Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Huang S / Xu P / Shen DD / Simon IA / Mao C / Tan Y / Zhang H / Harpsoe K / Li H / Zhang Y ...Huang S / Xu P / Shen DD / Simon IA / Mao C / Tan Y / Zhang H / Harpsoe K / Li H / Zhang Y / You C / Yu X / Jiang Y / Gloriam DE / Xu HE | |||||||||
Funding support | ![]()
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![]() | ![]() Title: GPCRs steer G and G selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors. Authors: Sijie Huang / Peiyu Xu / Dan-Dan Shen / Icaro A Simon / Chunyou Mao / Yangxia Tan / Huibing Zhang / Kasper Harpsøe / Huadong Li / Yumu Zhang / Chongzhao You / Xuekui Yu / Yi Jiang / Yan ...Authors: Sijie Huang / Peiyu Xu / Dan-Dan Shen / Icaro A Simon / Chunyou Mao / Yangxia Tan / Huibing Zhang / Kasper Harpsøe / Huadong Li / Yumu Zhang / Chongzhao You / Xuekui Yu / Yi Jiang / Yan Zhang / David E Gloriam / H Eric Xu / ![]() ![]() ![]() Abstract: Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of G, G or G proteins. The ...Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of G, G or G proteins. The structural basis for G protein subtype selectivity by these GPCRs remains elusive. Here, we report the structures of the serotonin receptors 5-HT, 5-HT, and 5-HT with G, and 5-HT with G. The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine receptor's selectivity for G and G, respectively. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures. Furthermore, we discover specific residues within TM5 and TM6 that function as micro-switches to form specific interactions with G or G. Together, these results present a common mechanism of G versus G protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin receptors. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 26.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20 KB 20 KB | Display Display | ![]() |
Images | ![]() | 84.2 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
Others | ![]() ![]() | 23.2 MB 23.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 666.3 KB | Display | ![]() |
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Full document | ![]() | 665.8 KB | Display | |
Data in XML | ![]() | 10.6 KB | Display | |
Data in CIF | ![]() | 12.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xtaMC ![]() 7xt8C ![]() 7xt9C ![]() 7xtbC ![]() 7xtcC 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: 1.071 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33444_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33444_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Serotonin 4 (5-HT4) receptor-Gi-scFv16 complex
Entire | Name: Serotonin 4 (5-HT4) receptor-Gi-scFv16 complex |
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Components |
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-Supramolecule #1: Serotonin 4 (5-HT4) receptor-Gi-scFv16 complex
Supramolecule | Name: Serotonin 4 (5-HT4) receptor-Gi-scFv16 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
-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: ![]() |
Molecular weight | Theoretical: 40.414047 KDa |
Recombinant expression | Organism: ![]() |
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 UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-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: 37.915496 KDa |
Recombinant expression | Organism: ![]() |
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 UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: ![]() ![]() |
Molecular weight | Theoretical: 26.597682 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDVQLVESGG GLVQPGGSRK LSCSASGFAF SSFGMHWVRQ APEKGLEWVA YISSGSGTIY YADTVKGRFT ISRDDPKNTL FLQMTSLRS EDTAMYYCVR SIYYYGSSPF DFWGQGTTLT VSSGGGGSGG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH ...String: MDVQLVESGG GLVQPGGSRK LSCSASGFAF SSFGMHWVRQ APEKGLEWVA YISSGSGTIY YADTVKGRFT ISRDDPKNTL FLQMTSLRS EDTAMYYCVR SIYYYGSSPF DFWGQGTTLT VSSGGGGSGG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH SNGNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TF GAGTKLE LK |
-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: Soluble cytochrome b562,5-hydroxytryptamine receptor 4
Macromolecule | Name: Soluble cytochrome b562,5-hydroxytryptamine receptor 4 type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 59.525551 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DYKDDDDAKL QTMHHHHHHH HHHADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFD ILVGQIDDAL KLANEGKVKE AQAAAEQLKT TRNAYIQKYL ASENLYFQGG TDKLDANVSS EEGFGSVEKV V LLTFLSTV ...String: DYKDDDDAKL QTMHHHHHHH HHHADLEDNW ETLNDNLKVI EKADNAAQVK DALTKMRAAA LDAQKATPPK LEDKSPDSPE MKDFRHGFD ILVGQIDDAL KLANEGKVKE AQAAAEQLKT TRNAYIQKYL ASENLYFQGG TDKLDANVSS EEGFGSVEKV V LLTFLSTV ILMAILGNLL VMVAVCWDRQ LRKIKTNYFI VSLAFADLLV SVLVMPFGAI ELVQDIWIYG EVFCLVRTSL DV LLTTASI FHLCCISLDR YYAICCQPLV YRNKMTPLRI ALMLGGCWVI PTFISFLPIM QGWNNIGIID LIEKRKFNQN SNS TYCVFM VNKPYAITCS VVAFYIPFLL MVLAYYRIYV TAKEHAHQIQ MLQRAGASSE SRPQSADQHS THRMRTETKA AKTL CIIMG CFCLCWAPFF VTNIVDPFID YTVPGQVWTA FLWLGYINSG LNPFLYAFLN KSFRRAFLII LCCDDERYRR PSILG QTVP CSTTTINGST HVLRDAVECG GQWESQCHPP ATSPLVAAQP SDT UniProtKB: Soluble cytochrome b562, 5-hydroxytryptamine receptor 4 |
-Macromolecule #6: SEROTONIN
Macromolecule | Name: SEROTONIN / type: ligand / ID: 6 / Number of copies: 1 / Formula: SRO |
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Molecular weight | Theoretical: 176.215 Da |
Chemical component information | ![]() ChemComp-SRO: |
-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: 7.4 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
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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: 70.0 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 |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 611883 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |