[English] 日本語
Yorodumi
- PDB-9m1h: Cryo-EM structure of PGE2-EP1-Gq complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9m1h
TitleCryo-EM structure of PGE2-EP1-Gq complex
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Prostaglandin E2 receptor EP1 subtype
KeywordsMEMBRANE PROTEIN / GPCR / EP1 / PGE2 / Gq
Function / homology
Function and homology information


prostaglandin E receptor activity / Prostanoid ligand receptors / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / regulation of platelet activation / entrainment of circadian clock / regulation of canonical Wnt signaling pathway ...prostaglandin E receptor activity / Prostanoid ligand receptors / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / regulation of platelet activation / entrainment of circadian clock / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / phototransduction, visible light / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / photoreceptor outer segment / neuropeptide signaling pathway / D1 dopamine receptor binding / intracellular transport / postsynaptic cytosol / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / adenylate cyclase inhibitor activity / activation of adenylate cyclase activity / Hedgehog 'off' state / positive regulation of protein localization to cell cortex / T cell migration / adenylate cyclase-activating adrenergic receptor signaling pathway / Adenylate cyclase inhibitory pathway / enzyme regulator activity / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to glucagon stimulus / regulation of insulin secretion / cellular response to forskolin / GTPase activator activity / regulation of mitotic spindle organization / adenylate cyclase activator activity / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / trans-Golgi network membrane / Regulation of insulin secretion / negative regulation of inflammatory response to antigenic stimulus / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / bone development / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / platelet aggregation / centriolar satellite / G-protein beta/gamma-subunit complex binding / cognition / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / blood coagulation / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / 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 / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / sensory perception of smell / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / 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
Similarity search - Function
Prostanoid EP1 receptor / Prostaglandin DP receptor / Prostanoid receptor / G-protein alpha subunit, group Q / G-protein alpha subunit, group S / G-protein alpha subunit, group I / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. ...Prostanoid EP1 receptor / Prostaglandin DP receptor / Prostanoid receptor / G-protein alpha subunit, group Q / G-protein alpha subunit, group S / G-protein alpha subunit, group I / 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
Chem-P2E / Prostaglandin E2 receptor EP1 subtype / Guanine nucleotide-binding protein G(q) subunit alpha / 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 / Guanine nucleotide-binding protein G(i) subunit alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.55 Å
AuthorsMeng, X. / Xu, Y. / Xu, H.E.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81902085 China
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: Structural insights into the activation of the human prostaglandin E receptor EP1 subtype by prostaglandin E.
Authors: Xue Meng / Yang Li / Jiuyin Xu / Kai Wu / Wen Hu / Canrong Wu / H Eric Xu / Youwei Xu /
Abstract: Prostaglandin E (PGE) mediates diverse physiological processes through four G protein-coupled receptor subtypes (EP1-EP4). While structures of EP2, EP3, and EP4 have been determined, the structural ...Prostaglandin E (PGE) mediates diverse physiological processes through four G protein-coupled receptor subtypes (EP1-EP4). While structures of EP2, EP3, and EP4 have been determined, the structural basis for PGE recognition and activation of the EP1 receptor subtype has remained elusive due to its inherent instability. Here, we present the cryoelectron microscopy structure of the human EP1 receptor in complex with PGE and heterotrimeric Gq protein at 2.55 Å resolution, completing the structural characterization of the EP receptor family. Our structure reveals a unique binding mode of PGE within EP1, involving key interactions with residues in the orthosteric pocket. Notably, we observe a less pronounced outward displacement of transmembrane helix 6 compared to other EP receptor subtypes, suggesting a distinct activation mechanism for EP1. Through extensive mutational analyses, we identify critical residues involved in PGE recognition, EP1 activation, and Gq protein coupling. By overcoming the challenges associated with the instability of EP1, our findings provide valuable insights into the subtype-specific activation mechanisms of EP receptors and lay the foundation for the development of more selective EP1-targeted therapeutics.
History
DepositionFeb 26, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Apr 30, 2025Provider: repository / Type: Initial release
Revision 1.0Apr 30, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 30, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 30, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 30, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 30, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Nov 12, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Prostaglandin E2 receptor EP1 subtype
B: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(q) subunit alpha
C: 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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)129,7015
Polymers129,3484
Non-polymers3521
Water181
1


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

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Prostaglandin E2 receptor EP1 subtype / PGE receptor EP1 subtype / PGE2 receptor EP1 subtype / Prostanoid EP1 receptor


Mass: 41847.230 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTGER1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P34995

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

#2: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(q) subunit alpha / Adenylate cyclase-inhibiting G alpha protein / Adenylate cyclase-stimulating G alpha protein / ...Adenylate cyclase-inhibiting G alpha protein / Adenylate cyclase-stimulating G alpha protein / Guanine nucleotide-binding protein alpha-q


Mass: 41724.383 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1, GNAS, GNAS1, GSP, GNAQ, GAQ / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P63096, UniProt: P63092, UniProt: P50148, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37915.496 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7861.143 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768

-
Non-polymers , 2 types, 2 molecules

#5: Chemical ChemComp-P2E / (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / Prostaglandin E2


Mass: 352.465 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H32O5
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestN
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: PGE2-EP1-Gq complex / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
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: 5000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 30 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: NONE
3D reconstructionResolution: 2.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 543885 / 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