[English] 日本語
Yorodumi
- PDB-9dyd: Asenapine-bound serotonin 1A (5-HT1A) receptor-Goa protein complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9dyd
TitleAsenapine-bound serotonin 1A (5-HT1A) receptor-Goa protein complex
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Soluble cytochrome b562,5-hydroxytryptamine receptor 1A
KeywordsSIGNALING PROTEIN / GPCR Signaling Complex / Serotonin Receptor
Function / homology
Function and homology information


regulation of serotonin secretion / Gi/o-coupled serotonin receptor activity / regulation of hormone secretion / regulation of behavior / receptor-receptor interaction / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / regulation of dopamine metabolic process / serotonin receptor signaling pathway ...regulation of serotonin secretion / Gi/o-coupled serotonin receptor activity / regulation of hormone secretion / regulation of behavior / receptor-receptor interaction / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / regulation of dopamine metabolic process / serotonin receptor signaling pathway / neurotransmitter receptor activity / mu-type opioid receptor binding / serotonin metabolic process / corticotropin-releasing hormone receptor 1 binding / serotonin binding / vesicle docking involved in exocytosis / G protein-coupled dopamine receptor signaling pathway / gamma-aminobutyric acid signaling pathway / regulation of heart contraction / parallel fiber to Purkinje cell synapse / exploration behavior / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of vasoconstriction / behavioral fear response / postsynaptic modulation of chemical synaptic transmission / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / muscle contraction / locomotory behavior / negative regulation of insulin secretion / electron transport chain / GABA-ergic synapse / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / 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 / 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / 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 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / 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 / cell body / presynaptic membrane / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / chemical synaptic transmission / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (q) signalling events / Ras protein signal transduction / postsynaptic membrane / periplasmic space / electron transfer activity / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / iron ion binding / lysosomal membrane / GTPase activity / positive regulation of cell population proliferation / heme binding / dendrite
Similarity search - Function
5-Hydroxytryptamine 1A receptor / 5-hydroxytryptamine receptor family / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit ...5-Hydroxytryptamine 1A receptor / 5-hydroxytryptamine receptor family / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / 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 / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / 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
: / CHOLESTEROL / Chem-J40 / 5-hydroxytryptamine receptor 1A / Guanine nucleotide-binding protein G(o) subunit alpha / Soluble cytochrome b562 / 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
Similarity search - Component
Biological speciesHomo sapiens (human)
Escherichia coli (E. coli)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.96 Å
AuthorsWarren, A.L. / Zilberg, G. / Wacker, D.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM 133504 United States
Other privateMcKnight Foundation
Other privateIrma T. Hirschl/Monique Weill-Caulier Trust
CitationJournal: Sci Adv / Year: 2025
Title: Structural determinants of G protein subtype selectivity at the serotonin receptor 5-HT1A.
Authors: Audrey L Warren / Gregory Zilberg / Anwar Abbassi / Alejandro Abraham / Shifan Yang / Daniel Wacker /
Abstract: Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the ...Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the receptor signals through inhibitory G proteins, more work is necessary to understand differences in transducer coupling and its relation to functional activity. To develop a molecular understanding of the differences underlying transducer coupling and activation, we performed structure-activity relationship studies of 5-HT1A with distinct G proteins. Through a combination of in vitro assays, we identified a potent partial agonist that selectively engages a G protein subtype. We further investigated the differences in G protein engagement at 5-HT1A with cryo-electron microscopy, determining structures of 5-HT1A bound to distinct ligands and G protein subtypes. Combined with subsequent structure-guided mutagenesis and signaling assays, our studies uncover both orthosteric and allosteric determinants of agonist-specific stimulation of distinct transducers.
History
DepositionOct 14, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 13, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(o) subunit alpha
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
R: Soluble cytochrome b562,5-hydroxytryptamine receptor 1A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)151,7029
Polymers149,4014
Non-polymers2,3015
Water00
1


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

-
Components

-
Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG

#1: Protein Guanine nucleotide-binding protein G(o) subunit alpha


Mass: 40100.500 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAO1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P09471, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 39418.086 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 8506.765 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768

-
Protein , 1 types, 1 molecules R

#4: Protein Soluble cytochrome b562,5-hydroxytryptamine receptor 1A


Mass: 61375.930 Da / Num. of mol.: 1 / Fragment: residues 1-25 of the 5-HT receptor deleted / Mutation: L125W
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human)
Gene: cybC, HTR1A, ADRB2RL1, ADRBRL1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P0ABE7, UniProt: P08908

-
Non-polymers , 3 types, 5 molecules

#5: Chemical ChemComp-A1BIR / (3aS,12bR)-asenapine / (3aS,12bR)-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole


Mass: 285.768 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H16ClNO / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C27H46O
#7: Chemical ChemComp-J40 / [(2R)-1-[oxidanyl-[(2R,3R,5S,6R)-2,3,5,6-tetrakis(oxidanyl)-4-phosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-3-tetradecanoyloxy-propan-2-yl] (5E,8E)-hexadeca-5,8,11,14-tetraenoate


Mass: 854.895 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C39H68O16P2

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

Component
IDNameTypeDetailsEntity IDParent-IDSource
1Serotonin 1A (5-HT1A) receptor-Goa protein complexCOMPLEXSerotonin 1A (5-HT1A) receptor-Goa protein complex with components purified separately and assembled in vitro.#1-#40MULTIPLE SOURCES
2Goa proteinCOMPLEX#1-#31RECOMBINANT
3Serotonin 1A (5-HT1A) receptor chimeraCOMPLEX#41RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Homo sapiens (human)9606
33Escherichia coli (E. coli)562
43Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDPlasmid
22Spodoptera frugiperda (fall armyworm)7108pFB
33Spodoptera frugiperda (fall armyworm)7108
Buffer solutionpH: 7.4
Buffer component
IDConc.NameBuffer-ID
120 mMHEPES1
2100 mMsodium chloride1
30.001 % (w/v)LMNG1
40.0001 % (w/v)CHS1
50.0001 % (w/v)GDN1
SpecimenConc.: 18 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Sample was mono disperse following gel filtration. The sample was immediately concentrated for CryoEM grid preparation.
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil
VitrificationInstrument: LEICA EM GP / Cryogen name: ETHANE
Details: Blot force 3 for 3-5 seconds was used and subsequent grids were screened for ice thickness prior to data collection.

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 51.43 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 11535

-
Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
2Leginonimage acquisition
4cryoSPARCCTF correction
7UCSF Chimeramodel fitting
9PHENIXmodel refinement
10Cootmodel refinement
11REFMACmodel refinement
13cryoSPARCfinal Euler assignment
14cryoSPARCclassification
15cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 16437128
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 2.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 791392 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more