[English] 日本語
Yorodumi
- PDB-25nx: A complex of PTH1R/Gs bound to a PTHrP analogue with three beta-a... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 25nx
TitleA complex of PTH1R/Gs bound to a PTHrP analogue with three beta-amino acids
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Nanobody35
  • Parathyroid hormone/parathyroid hormone-related peptide receptor
  • Peptide 2 (PTHrP analogue)
KeywordsMEMBRANE PROTEIN / GPCR / g protein / agonist / parathyroid
Function / homology
Function and homology information


parathyroid hormone receptor activity / G protein-coupled peptide receptor activity / Class B/2 (Secretin family receptors) / osteoblast development / bone mineralization / positive regulation of inositol phosphate biosynthetic process / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / peptide hormone binding / regulation of skeletal muscle contraction ...parathyroid hormone receptor activity / G protein-coupled peptide receptor activity / Class B/2 (Secretin family receptors) / osteoblast development / bone mineralization / positive regulation of inositol phosphate biosynthetic process / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / peptide hormone binding / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / chondrocyte differentiation / intracellular transport / bone resorption / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to acidic pH / cell maturation / cellular response to glucagon stimulus / intracellular glucose homeostasis / adenylate cyclase activator activity / positive regulation of insulin secretion involved in cellular response to glucose stimulus / trans-Golgi network membrane / skeletal system development / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / bone development / platelet aggregation / cognition / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / intracellular calcium ion homeostasis / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / positive regulation of insulin secretion / Olfactory Signaling Pathway / 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 / sensory perception of smell / Glucagon signaling in metabolic regulation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / photoreceptor disc membrane / 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 / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / 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 / positive regulation of cold-induced thermogenesis / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / retina development in camera-type eye / GTPase binding / fibroblast proliferation / G protein activity / Ca2+ pathway / 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 / in utero embryonic development / phospholipase C-activating G protein-coupled receptor signaling pathway / basolateral plasma membrane / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / cell surface receptor signaling pathway / signaling receptor complex / Extra-nuclear estrogen signaling / cell population proliferation
Similarity search - Function
GPCR, family 2, parathyroid hormone receptor / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site ...GPCR, family 2, parathyroid hormone receptor / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / 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 / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / 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
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 / Parathyroid hormone/parathyroid hormone-related peptide receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
Lama glama (llama)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.86 Å
AuthorsCary, B.P. / Wootten, D. / Sexton, P.M. / Gellman, S.H. / Wook, T.K. / Shin, J. / Gerrard, E.J.
Funding support Australia, United States, 4items
OrganizationGrant numberCountry
Australian Research Council (ARC)DE250101183 Australia
National Health and Medical Research Council (NHMRC, Australia)2025694 Australia
National Health and Medical Research Council (NHMRC, Australia)2026300 Australia
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM151985 United States
CitationJournal: J Am Chem Soc / Year: 2026
Title: Altered Intracellular Trafficking as a Mechanism for Prolonged Duration of G Protein-Coupled Receptor Activation.
Authors: Tae Wook Kim / Elliot J Gerrard / Jeeeun Shin / Thomas J Gardella / Denise Wootten / Patrick M Sexton / Brian P Cary / Samuel H Gellman /
Abstract: G protein-coupled receptors (GPCRs) mediate information transfer to cells from the surrounding environment. In most cases, signaling is initiated or amplified when the receptor binds to an agonist, ...G protein-coupled receptors (GPCRs) mediate information transfer to cells from the surrounding environment. In most cases, signaling is initiated or amplified when the receptor binds to an agonist, an event that alters the conformational profile of the receptor. Signal transduction results from interaction between the agonist-receptor complex and cytosolic partners such as G proteins, GPCR kinases (GRKs), and β-arrestins. Changes in agonist structure can lead to "signal bias", i.e., changes in the relative strength of signaling involving different partners. Some GPCRs, including those activated by long peptide hormones, continue to signal after internalization. In these cases, changes in agonist structure can lead to changes in the relative extent of signaling from different sites, e.g., cell surface vs endosomes ("location bias"). Many GPCRs are targets of approved drugs or drug candidates, and tuning signal bias and/or location bias is widely considered to be important for optimizing therapeutic profiles. Here we report another mechanism of modulating outcome via agonist modification: alteration of intracellular trafficking. The synthetic peptide agonist designated SPT, which contains five β-amino acid residues, was previously shown to activate the parathyroid hormone receptor-1 (PTH1R) and cause prolonged signaling in mice by an unknown mechanism. The SPT-PTH1R complex continues to stimulate cAMP production after internalization. We now find that the SPT-PTH1R complex impairs the sorting of early endosomes into recycling endosomes relative to the receptor complexed to the drug teriparatide. These findings suggest that altering intracellular GPCR trafficking patterns represents an unappreciated strategy for achieving prolonged action .
History
DepositionApr 10, 2026Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jun 3, 2026Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Jun 3, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
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
N: Nanobody35
P: Peptide 2 (PTHrP analogue)
R: Parathyroid hormone/parathyroid hormone-related peptide receptor


Theoretical massNumber of molelcules
Total (without water)180,1926
Polymers180,1926
Non-polymers00
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(s) subunit alpha isoforms short / Adenylate cyclase-stimulating G alpha protein


Mass: 45699.434 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P63092
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37413.863 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
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 6375.332 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

-
Antibody / Protein/peptide / Protein , 3 types, 3 molecules NPR

#4: Antibody Nanobody35


Mass: 16926.076 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli)
#5: Protein/peptide Peptide 2 (PTHrP analogue)


Mass: 4263.860 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#6: Protein Parathyroid hormone/parathyroid hormone-related peptide receptor / PTH/PTHrP type I receptor / PTH/PTHr receptor / Parathyroid hormone 1 receptor / PTH1 receptor


Mass: 69513.758 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTH1R, PTHR, PTHR1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q03431

-
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

ComponentName: Complex of PTH1R/Gs bound to a modified PTHrP analogue
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 0.15 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1400 nm / Nominal defocus min: 700 nm
Specimen holderCryogen: NITROGEN
Image recordingAverage exposure time: 6.59 sec. / Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 6463

-
Processing

EM software
IDNameVersionCategory
1cryoSPARC4.6.0particle selection
2EPUimage acquisition
4cryoSPARC4.6.0CTF correction
9cryoSPARC4.6.0initial Euler assignment
10cryoSPARC4.6.0final Euler assignment
12cryoSPARC4.6.03D reconstruction
13PHENIX1.19.2model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 3160548
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 2.86 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 336618 / Symmetry type: POINT
Atomic model buildingSpace: REAL

+
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