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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | Serotonin 4 (5-HT4) receptor-Gi-scFv16 complex | |||||||||
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Keywords | 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 | Function and homology informationlarge intestinal transit / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of appetite / maintenance of gastrointestinal epithelium / mucus secretion / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / serotonin binding ...large intestinal transit / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of appetite / maintenance of gastrointestinal epithelium / mucus secretion / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / serotonin binding / regulation of postsynapse assembly / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to forskolin / regulation of mitotic spindle organization / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / electron transport chain / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / centriolar satellite / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / GTPase binding / Ca2+ pathway / fibroblast proliferation / midbody / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / chemical synaptic transmission / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / periplasmic space / electron transfer activity / Extra-nuclear estrogen signaling / cell population proliferation / postsynapse / endosome membrane / ciliary basal body / G protein-coupled receptor signaling pathway / iron ion binding / lysosomal membrane / cell division / GTPase activity Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | 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 | China, 1 items
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Citation | Journal: Mol Cell / Year: 2022Title: 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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_33444.map.gz | 26.4 MB | EMDB map data format | |
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| Header (meta data) | emd-33444-v30.xml emd-33444.xml | 20 KB 20 KB | Display Display | EMDB header |
| Images | emd_33444.png | 84.2 KB | ||
| Filedesc metadata | emd-33444.cif.gz | 6.6 KB | ||
| Others | emd_33444_half_map_1.map.gz emd_33444_half_map_2.map.gz | 23.2 MB 23.2 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33444 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33444 | 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 F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_33444.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| 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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| 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: Homo sapiens (human) |
-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: Trichoplusia ni (cabbage looper) |
| 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: Homo sapiens (human) |
| Molecular weight | Theoretical: 37.915496 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| 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: Trichoplusia ni (cabbage looper) |
| 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: Homo sapiens (human) |
| Molecular weight | Theoretical: 7.861143 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| 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: Homo sapiens (human) |
| Molecular weight | Theoretical: 59.525551 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| 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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Processing | 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: FIELD EMISSION GUN |
| 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 |
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Keywords
Homo sapiens (human)
Authors
China, 1 items
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Y (Row.)
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Trichoplusia ni (cabbage looper)
FIELD EMISSION GUN
