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- PDB-9ugl: Cryo-EM structure of 5-HT2CR. -

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Basic information

Entry
Database: PDB / ID: 9ugl
TitleCryo-EM structure of 5-HT2CR.
Components5-hydroxytryptamine receptor 2C
KeywordsMEMBRANE PROTEIN / 5HTR
Function / homology
Function and homology information


regulation of corticotropin-releasing hormone secretion / regulation of appetite / 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 / regulation of nervous system process / phospholipase C-activating serotonin receptor signaling pathway / serotonin receptor activity ...regulation of corticotropin-releasing hormone secretion / regulation of appetite / 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 / regulation of nervous system process / phospholipase C-activating serotonin receptor signaling pathway / serotonin receptor activity / Serotonin receptors / G protein-coupled serotonin receptor activity / serotonin receptor signaling pathway / neurotransmitter receptor activity / serotonin binding / feeding behavior / : / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of fat cell differentiation / behavioral fear response / release of sequestered calcium ion into cytosol / positive regulation of calcium-mediated signaling / locomotory behavior / intracellular calcium ion homeostasis / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of ERK1 and ERK2 cascade / synapse / dendrite / identical protein binding / plasma membrane
Similarity search - Function
5-Hydroxytryptamine 2C receptor / 5-hydroxytryptamine receptor family / Serpentine type 7TM GPCR chemoreceptor Srsx / 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.
Similarity search - Domain/homology
: / 5-hydroxytryptamine receptor 2C
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.65 Å
AuthorsParajulee, A. / Kim, K.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: Structure of membrane protein
Authors: Parajulee, A. / Kim, K.
History
DepositionApr 12, 2025Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 15, 2026Provider: repository / Type: Initial release
Revision 1.0Apr 15, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 15, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 15, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 15, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 15, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: 5-hydroxytryptamine receptor 2C
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,3102
Polymers45,9151
Non-polymers3951
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein 5-hydroxytryptamine receptor 2C / 5-HT-2C / 5-HT2C / 5-HTR2C / 5-hydroxytryptamine receptor 1C / 5-HT-1C / 5-HT1C / Serotonin receptor 2C


Mass: 45915.184 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HTR2C, HTR1C / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P28335
#2: Chemical ChemComp-A1L83 / SB-242084 / 6-chloranyl-5-methyl-~{N}-[6-(2-methylpyridin-3-yl)oxypyridin-3-yl]-2,3-dihydroindole-1-carboxamide


Mass: 394.854 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H19ClN4O2
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Complex of receptor with BRIL, anti-BRIL Fab and anti-Fab nanobody
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.15 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenConc.: 8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 277 K

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Num. of real images: 13717
EM imaging opticsEnergyfilter slit width: 20 eV
Image scansWidth: 5760 / Height: 4092

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2EPUimage acquisition
7UCSF Chimera1.17.3model fitting
9PHENIX1.21.2.5419model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1864086
3D reconstructionResolution: 2.65 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 402295 / Algorithm: FOURIER SPACE / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT
Atomic model buildingPDB-ID: 6BQH

6bqh


Pdb chain-ID: A / Accession code: 6BQH / Chain residue range: 46-387 / Pdb chain residue range: 46-387 / Source name: PDB / Type: experimental model
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 108.99 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00322063
ELECTRON MICROSCOPYf_angle_d0.58662836
ELECTRON MICROSCOPYf_chiral_restr0.0426363
ELECTRON MICROSCOPYf_plane_restr0.0039336
ELECTRON MICROSCOPYf_dihedral_angle_d3.7051283

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