[English] 日本語
Yorodumi
- EMDB-36409: ST1936-5HT6R complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-36409
TitleST1936-5HT6R complex
Map dataThis is the cryo-EM density of ST1936-ht6 complex.
Sample
  • Complex: st1936-HT6
    • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: Nb35
    • Protein or peptide: 5-hydroxytryptamine receptor 6
  • Ligand: 2-(5-chloranyl-2-methyl-1~{H}-indol-3-yl)-N,N-dimethyl-ethanamine
KeywordsGPCR / MEMBRANE PROTEIN
Function / homology
Function and homology information


adenylate cyclase-activating serotonin receptor signaling pathway / histamine receptor activity / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / cerebral cortex cell migration / PKA activation in glucagon signalling / developmental growth / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger ...adenylate cyclase-activating serotonin receptor signaling pathway / histamine receptor activity / Serotonin receptors / serotonin receptor activity / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / cerebral cortex cell migration / PKA activation in glucagon signalling / developmental growth / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / positive regulation of TOR signaling / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / activation of adenylate cyclase activity / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to glucagon stimulus / regulation of insulin secretion / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / bone development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / platelet aggregation / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / cognition / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / sensory perception of smell / 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) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / G protein activity / 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 / Extra-nuclear estrogen signaling / cell population proliferation / cilium / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / dendrite / synapse / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
5-Hydroxytryptamine 6 receptor / G-protein alpha subunit, group S / 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. ...5-Hydroxytryptamine 6 receptor / G-protein alpha subunit, group S / 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
5-hydroxytryptamine receptor 6 / 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 short
Similarity search - Component
Biological speciesHomo sapiens (human) / Camelus bactrianus (Bactrian camel)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.09 Å
AuthorsWen X / Sun J
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Biochem Biophys Res Commun / Year: 2023
Title: Structural insight into the selective agonist ST1936 binding of serotonin receptor 5-HT6.
Authors: Yuan Pei / Xin Wen / Sheng-Chao Guo / Zhi-Shuai Yang / Ru Zhang / Peng Xiao / Jin-Peng Sun /
Abstract: The serotonin receptor 5-HTR is an important G-protein-coupled receptor (GPCR) that involved in essential functions within the central and peripheral nervous systems and is linked to various ...The serotonin receptor 5-HTR is an important G-protein-coupled receptor (GPCR) that involved in essential functions within the central and peripheral nervous systems and is linked to various psychiatric disorders. Selective activation of 5-HTR promotes neural stem cell regeneration activity. As a 5-HTR selective agonist, 2-(5 chloro-2-methyl-1H-indol-3-yl)-N, N-dimethylethanolamine (ST1936) has been widely used to investigate the functions of the 5-HTR. The molecular mechanism of how ST1936 is recognized by 5-HTR and how it effectively couples with Gs remain unclear. Here, we reconstituted the ST1936-5-HTR-Gs complex in vitro and solved its cryo-electron microscopy structure at 3.1 Å resolution. Further structural analysis and mutational studies facilitated us to identify the residues of the Y310 and "toggle switch" W281 of the 5-HTR contributed to the higher efficacy of ST1936 compared with 5-HT. By uncovering the structural foundation of how 5-HTR specifically recognizes agonists and elucidating the molecular process of G protein activation, our discoveries offer valuable insights and pave the way for the development of promising 5-HTR agonists.
History
DepositionJun 4, 2023-
Header (metadata) releaseJun 28, 2023-
Map releaseJun 28, 2023-
UpdateOct 30, 2024-
Current statusOct 30, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_36409.png

Downloads & links

-
Map

FileDownload / File: emd_36409.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationThis is the cryo-EM density of ST1936-ht6 complex.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 200 pix.
= 170. Å		0.85 Å/pix.
x 200 pix.
= 170. Å		0.85 Å/pix.
x 200 pix.
= 170. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.0018105257 - 2.3484554
Average (Standard dev.)0.0041954922 (±0.050170623)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 170.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: This is the half1 map.

Fileemd_36409_half_map_1.map
AnnotationThis is the half1 map.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: This is the half2 map.

Fileemd_36409_half_map_2.map
AnnotationThis is the half2 map.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : st1936-HT6

EntireName: st1936-HT6
Components
  • Complex: st1936-HT6
    • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Protein or peptide: Nb35
    • Protein or peptide: 5-hydroxytryptamine receptor 6
  • Ligand: 2-(5-chloranyl-2-methyl-1~{H}-indol-3-yl)-N,N-dimethyl-ethanamine

-
Supramolecule #1: st1936-HT6

SupramoleculeName: st1936-HT6 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

MacromoleculeName: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 45.683434 KDa
Recombinant expressionOrganism: Baculovirus expression vector pFastBac1-HM
SequenceString: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...String:
MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQA DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL

UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

-
Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.418086 KDa
Recombinant expressionOrganism: Baculovirus expression vector pFastBac1-HM
SequenceString: 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

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

-
Macromolecule #3: 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
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 6.375332 KDa
Recombinant expressionOrganism: Baculovirus expression vector pFastBac1-HM
SequenceString:
NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFR

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

-
Macromolecule #4: Nb35

MacromoleculeName: Nb35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Camelus bactrianus (Bactrian camel)
Molecular weightTheoretical: 13.885439 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSS

-
Macromolecule #5: 5-hydroxytryptamine receptor 6

MacromoleculeName: 5-hydroxytryptamine receptor 6 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 46.99209 KDa
Recombinant expressionOrganism: Baculovirus expression vector pFastBac1-HM
SequenceString: MVPEPGPTAN STPAWGAGPP SAPGGSGWVA AALCVVIALT AAANSLLIAL ICTQPALRNT SNFFLVSLFT SDLMVGLVVM PPAMLNALY GRWVLARGLC LLWTAFDVMC CSASILNLCL ISLDRYLLIL SPLRYKLRMT PLRALALVLG AWSLAALASF L PLLLGWHE ...String:
MVPEPGPTAN STPAWGAGPP SAPGGSGWVA AALCVVIALT AAANSLLIAL ICTQPALRNT SNFFLVSLFT SDLMVGLVVM PPAMLNALY GRWVLARGLC LLWTAFDVMC CSASILNLCL ISLDRYLLIL SPLRYKLRMT PLRALALVLG AWSLAALASF L PLLLGWHE LGHARPPVPG QCRLLASLPF VLVASGLTFF LPSGAICFTY CRILLAARKQ AVQVASLTTG MASQASETLQ VP RTPRPGV ESADSRRLAT KHSRKALKAS LTLGILLGMF FVTWLPFFVA NIVQAVCDCI SPGLFDVLTW LGYCNSTMNP IIY PLFMRD FKRALGRFLP CPRCPRERQA SLASPSLRTS HSGPRPGLSL QQVLPLPLPP DSDSDSDAGS GGSSGLRLTA QLLL PGEAT QDPPLPTRAA AAVNFFNIDP AEPELRPHPL GIPTN

UniProtKB: 5-hydroxytryptamine receptor 6

-
Macromolecule #6: 2-(5-chloranyl-2-methyl-1~{H}-indol-3-yl)-N,N-dimethyl-ethanamine

MacromoleculeName: 2-(5-chloranyl-2-methyl-1~{H}-indol-3-yl)-N,N-dimethyl-ethanamine
type: ligand / ID: 6 / Number of copies: 1 / Formula: UQL
Molecular weightTheoretical: 236.74 Da
Chemical component information

ChemComp-UQL:
2-(5-chloranyl-2-methyl-1~{H}-indol-3-yl)-N,N-dimethyl-ethanamine

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

7xtb

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.09 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 286776
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

+
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