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- EMDB-68650: 5HT2AR-miniGq heterotrimer in complex with a novel agonist IHCH-8152 -

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Basic information

Entry
Database: EMDB / ID: EMD-68650
Title5HT2AR-miniGq heterotrimer in complex with a novel agonist IHCH-8152
Map data
Sample
  • Complex: 5-HT2A receptor bound to IHCH-8152 in complex with a mini-Gq protein and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM)
    • Protein or peptide: 5-hydroxytryptamine receptor 2A
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: single-chain variable fragment 16 (scFv16)
  • Ligand: ~{N}-(3-azanylcyclobutyl)-2-(4-hexoxyphenyl)-~{N}-methyl-ethanamide
KeywordsGPCR / serotonin receptor / MEMBRANE PROTEIN / 5HT2AR
Function / homology
Function and homology information


positive regulation of heat generation / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / neurofilament / cell body fiber / artery smooth muscle contraction / positive regulation of cytokine production involved in immune response ...positive regulation of heat generation / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / neurofilament / cell body fiber / artery smooth muscle contraction / positive regulation of cytokine production involved in immune response / sensitization / Serotonin receptors / phospholipase C-activating serotonin receptor signaling pathway / G protein-coupled serotonin receptor activity / serotonin receptor signaling pathway / sensory perception of chemical stimulus / urinary bladder smooth muscle contraction / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / serotonin binding / positive regulation of platelet aggregation / negative regulation of synaptic transmission, glutamatergic / beta-2 adrenergic receptor binding / neurotransmitter receptor activity / positive regulation of DNA biosynthetic process / negative regulation of potassium ion transport / temperature homeostasis / detection of temperature stimulus involved in sensory perception of pain / developmental growth / PKA activation in glucagon signalling / detection of mechanical stimulus involved in sensory perception of pain / positive regulation of vasoconstriction / regulation of dopamine secretion / positive regulation of execution phase of apoptosis / protein tyrosine kinase activator activity / D1 dopamine receptor binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Hedgehog 'off' state / release of sequestered calcium ion into cytosol / insulin-like growth factor receptor binding / behavioral response to cocaine / presynaptic modulation of chemical synaptic transmission / ionotropic glutamate receptor binding / adenylate cyclase activator activity / bone development / dendritic shaft / memory / platelet aggregation / caveola / intracellular calcium ion homeostasis / G-protein beta/gamma-subunit complex binding / positive regulation of neuron apoptotic process / Olfactory Signaling Pathway / positive regulation of inflammatory response / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / 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 / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / heterotrimeric G-protein complex / positive regulation of cold-induced thermogenesis / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / GPER1 signaling / presynapse / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / positive regulation of cytosolic calcium ion concentration / Thrombin signalling through proteinase activated receptors (PARs) / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / chemical synaptic transmission / GTPase binding / cytoplasmic vesicle / presynaptic membrane / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
Similarity search - Function
5-Hydroxytryptamine 2A receptor / 5-hydroxytryptamine receptor family / G-protein alpha subunit, group S / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit ...5-Hydroxytryptamine 2A receptor / 5-hydroxytryptamine receptor family / G-protein alpha subunit, group S / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / Guanine nucleotide-binding protein, beta subunit / G protein beta WD-40 repeat protein / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
5-hydroxytryptamine receptor 2A / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsTang L / Cao M / Li H / Meng B / Liu Z / Cheng J / Wang S
Funding support China, 6 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)82225045 China
Other governmentMinistry of Science and Technology of China (2020YFA0509600 to S.W.)
National Natural Science Foundation of China (NSFC)22177074 China
National Natural Science Foundation of China (NSFC)22377077 China
Other governmentProgram of Shanghai Academic/Technology Research Leader (22XD1421900 to J.C.)
Other governmentShanghai Municipal Government and ShanghaiTech University (to J.C.)
CitationJournal: To Be Published
Title: Mechanisms Underlying Sustained Antidepressant Effects of Psychedelics Inspire Microdosing Strategies
Authors: He L / Tang L / Cao D / Duan W / Yu J / Zhang P / Li H / Wang Y / Meng B / Wang H / Zhou Y / Li W / Li X / Liu Z / Zhang L / Li L / Cheng J / Wang S
History
DepositionJan 22, 2026-
Header (metadata) releaseOct 21, 2026-
Map releaseOct 21, 2026-
UpdateOct 21, 2026-
Current statusOct 21, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_68650.png

Downloads & links

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Map

FileDownload / File: emd_68650.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.33 Å/pix.
x 200 pix.
= 266.24 Å		1.33 Å/pix.
x 200 pix.
= 266.24 Å		1.33 Å/pix.
x 200 pix.
= 266.24 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.3312 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.23
Minimum - Maximum-1.8718418 - 3.167724
Average (Standard dev.)-0.0010831836 (±0.054165978)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 266.24 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_68650_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_68650_half_map_2.map
Projections & Slices
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Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : 5-HT2A receptor bound to IHCH-8152 in complex with a mini-Gq prot...

EntireName: 5-HT2A receptor bound to IHCH-8152 in complex with a mini-Gq protein and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM)
Components
  • Complex: 5-HT2A receptor bound to IHCH-8152 in complex with a mini-Gq protein and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM)
    • Protein or peptide: 5-hydroxytryptamine receptor 2A
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: single-chain variable fragment 16 (scFv16)
  • Ligand: ~{N}-(3-azanylcyclobutyl)-2-(4-hexoxyphenyl)-~{N}-methyl-ethanamide

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Supramolecule #1: 5-HT2A receptor bound to IHCH-8152 in complex with a mini-Gq prot...

SupramoleculeName: 5-HT2A receptor bound to IHCH-8152 in complex with a mini-Gq protein and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: 5-hydroxytryptamine receptor 2A

MacromoleculeName: 5-hydroxytryptamine receptor 2A / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.50727 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GPGSGSGLSL LHLQEKNWSA LLTAVVIILT IAGNILVIMA VSLEKKLQNA TNYFLMSLAI ADMLLGFLVM PVSMLTILYG YRWPLPSKL CAVWIYLDVL FSTASIMHLC AISLDRYVAI QNPIHHSRFN SRTKAFLKII AVWTISVGIS MPIPVFGLQD D SKVFKEGS ...String:
GPGSGSGLSL LHLQEKNWSA LLTAVVIILT IAGNILVIMA VSLEKKLQNA TNYFLMSLAI ADMLLGFLVM PVSMLTILYG YRWPLPSKL CAVWIYLDVL FSTASIMHLC AISLDRYVAI QNPIHHSRFN SRTKAFLKII AVWTISVGIS MPIPVFGLQD D SKVFKEGS CLLADDNFVL IGSFVSFFIP LTIMVITYFL TIKSLQKEAT LCVSDLGTRA KLASFSFLPQ SSLSSEKLFQ RS IHREPGS YTGRRTMQSI SNEQKACKVL GIVFFLFVVM WCPFFITNIM AVICKESCNE DVIGALLNVF VWIGYLSSAV NPL VYTLFN KTYRSAFSRY

UniProtKB: 5-hydroxytryptamine receptor 2A

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Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2...

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
EC number: Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 36.55859 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA MGCTVSAED KAAAERSKMI DKNLREDGEK ARRTLRLLLL GADNSGKSTI VKQMRILHGG SGGSGGTSGI FETKFQVDKV N FHMFDVGG ...String:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA MGCTVSAED KAAAERSKMI DKNLREDGEK ARRTLRLLLL GADNSGKSTI VKQMRILHGG SGGSGGTSGI FETKFQVDKV N FHMFDVGG QRDERRKWIQ CFNDVTAIIF VVDSSDYNRL QEALNLFKSI WNNRWLRTIS VILFLNKQDL LAEKVLAGKS KI EDYFPEF ARYTTPEDAT PEPGEDPRVT RAKYFIRDEF LRISTASGDG RHYCYPHFTC AVDTENARRI FAAVKDTILQ LNL REYNLV

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas

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Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: 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
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.342785 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String:
GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

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Macromolecule #4: single-chain variable fragment 16 (scFv16)

MacromoleculeName: single-chain variable fragment 16 (scFv16) / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 27.531625 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: 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 KAAAENLYFQ G

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Macromolecule #5: ~{N}-(3-azanylcyclobutyl)-2-(4-hexoxyphenyl)-~{N}-methyl-ethanamide

MacromoleculeName: ~{N}-(3-azanylcyclobutyl)-2-(4-hexoxyphenyl)-~{N}-methyl-ethanamide
type: ligand / ID: 5 / Number of copies: 1 / Formula: A1EEO
Molecular weightTheoretical: 318.454 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
GridModel: Quantifoil / Material: GOLD / Mesh: 300
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number real images: 8564 / Average exposure time: 2.0 sec. / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7ran

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: CCP4 package / Number images used: 791492
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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