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- EMDB-27634: Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to ps... -
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Open data
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Basic information
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Title | Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to psilocin | |||||||||
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Function / homology | ![]() regulation of corticotropin-releasing hormone secretion / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / regulation of appetite / regulation of nervous system process / Serotonin receptors ...regulation of corticotropin-releasing hormone secretion / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / regulation of appetite / regulation of nervous system process / Serotonin receptors / serotonin receptor signaling pathway / serotonin binding / G protein-coupled serotonin receptor activity / feeding behavior / neurotransmitter receptor activity / positive regulation of fat cell differentiation / cGMP-mediated signaling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / behavioral fear response / release of sequestered calcium ion into cytosol / positive regulation of calcium-mediated signaling / locomotory behavior / 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 / 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 / intracellular calcium ion homeostasis / 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 / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / 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 / positive regulation of ERK1 and ERK2 cascade / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / signal transduction / extracellular exosome / identical protein binding / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
![]() | Gumpper RH / Fay JF / Roth BL | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular insights into the regulation of constitutive activity by RNA editing of 5HT serotonin receptors. Authors: Ryan H Gumpper / Jonathan F Fay / Bryan L Roth / ![]() Abstract: RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT serotonin receptor, which undergoes ...RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 54.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.5 KB 21.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 75.5 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Others | ![]() ![]() ![]() | 60 MB 59.4 MB 59.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dpgMC ![]() 8dpfC ![]() 8dphC ![]() 8dpiC 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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Annotation | main map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.91 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Additional map: B factor sharp map
File | emd_27634_additional_1.map | ||||||||||||
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Annotation | B factor sharp map | ||||||||||||
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-Half map: half map B
File | emd_27634_half_map_1.map | ||||||||||||
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Annotation | half map B | ||||||||||||
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-Half map: half map A
File | emd_27634_half_map_2.map | ||||||||||||
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Annotation | half map A | ||||||||||||
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Sample components
-Entire : 5-ht2c heterotrimeric complex (INI isoform)
Entire | Name: 5-ht2c heterotrimeric complex (INI isoform) |
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Components |
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-Supramolecule #1: 5-ht2c heterotrimeric complex (INI isoform)
Supramolecule | Name: 5-ht2c heterotrimeric complex (INI isoform) / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: 5-hydroxytryptamine receptor 2C
Macromolecule | Name: 5-hydroxytryptamine receptor 2C / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 51.876066 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MVNLRNAVHS FLVHLIGLLV WQCDISVSPV AAIVTDIFNT SDGGRFKFPD GVQNWPALSI VIIIIMTIGG NILVIMAVSM EKKLHNATN YFLMSLAIAD MLVGLLVMPL SLLAILYDYV WPLPRYLCPV WISLDVLFST ASIMHLCAIS LDRYVAIRNP I EHSRFNSR ...String: MVNLRNAVHS FLVHLIGLLV WQCDISVSPV AAIVTDIFNT SDGGRFKFPD GVQNWPALSI VIIIIMTIGG NILVIMAVSM EKKLHNATN YFLMSLAIAD MLVGLLVMPL SLLAILYDYV WPLPRYLCPV WISLDVLFST ASIMHLCAIS LDRYVAIRNP I EHSRFNSR TKAIMKIAIV WAISIGVSVP IPVIGLRDEE KVFVNNTTCV LNDPNFVLIG SFVAFFIPLT IMVITYCLTI YV LRRQALM LLHGHTEEPP GLSLDFLKCC KRNTAEEENS ANPNQDQNAR RRKKKERRPR GTMQAINNER KASKVLGIVF FVF LIMWCP FFITNILSVL CEKSCNQKLM EKLLNVFVWI GYVCSGINPL VYTLFNKIYR RAFSNYLRCN YKVEKKPPVR QIPR VAATA LSGRELNVNI YRHTNEPVIE KASDNEPGIE MQVENLELPV NPSSVVSERI SSV |
-Macromolecule #2: G-alpha subunit q (Gi2-mini-Gq chimera)
Macromolecule | Name: G-alpha subunit q (Gi2-mini-Gq chimera) / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
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 #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.418086 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...String: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN |
-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 |
-Macromolecule #5: Antibody fragment scFv16
Macromolecule | Name: Antibody fragment scFv16 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 28.668922 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 KAAALEVLFQ GPHHHHHHHH |
-Macromolecule #6: 3-[2-(dimethylamino)ethyl]-1~{H}-indol-4-ol
Macromolecule | Name: 3-[2-(dimethylamino)ethyl]-1~{H}-indol-4-ol / type: ligand / ID: 6 / Number of copies: 1 / Formula: 91Q |
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Molecular weight | Theoretical: 204.268 Da |
Chemical component information | ![]() ChemComp-91Q: |
-Macromolecule #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 1 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-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 TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 49.5 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.6910000000000003 µm / Nominal defocus min: 0.1 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |