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- PDB-9ly2: A Cryo-EM structure of LA-PTH-PTH1R-V2RT-Beta-arrestin1 complex (... -

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Basic information

Entry
Database: PDB / ID: 9ly2
TitleA Cryo-EM structure of LA-PTH-PTH1R-V2RT-Beta-arrestin1 complex (state 1 conformation)
Components
  • Beta-arrestin-1
  • Fab30H
  • Fab30L
  • LA-PTH
  • Parathyroid hormone/parathyroid hormone-related peptide receptor,Vasopressin V2 receptor
KeywordsMEMBRANE PROTEIN / PTH1R / arrestin / GPCR
Function / homology
Function and homology information


renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / parathyroid hormone receptor activity / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / angiotensin receptor binding / TGFBR3 regulates TGF-beta signaling / hemostasis / Activation of SMO ...renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / parathyroid hormone receptor activity / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / angiotensin receptor binding / TGFBR3 regulates TGF-beta signaling / hemostasis / Activation of SMO / telencephalon development / negative regulation of interleukin-8 production / arrestin family protein binding / Class B/2 (Secretin family receptors) / G protein-coupled receptor internalization / G protein-coupled peptide receptor activity / osteoblast development / Lysosome Vesicle Biogenesis / : / stress fiber assembly / positive regulation of cardiac muscle hypertrophy / positive regulation of inositol phosphate biosynthetic process / Golgi Associated Vesicle Biogenesis / bone mineralization / positive regulation of Rho protein signal transduction / pseudopodium / positive regulation of systemic arterial blood pressure / negative regulation of interleukin-6 production / peptide hormone binding / positive regulation of intracellular signal transduction / positive regulation of receptor internalization / positive regulation of vasoconstriction / negative regulation of Notch signaling pathway / endocytic vesicle / chondrocyte differentiation / bone resorption / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / activation of adenylate cyclase activity / cellular response to hormone stimulus / insulin-like growth factor receptor binding / cell maturation / response to cytokine / clathrin-coated pit / negative regulation of protein ubiquitination / enzyme inhibitor activity / GTPase activator activity / Activated NOTCH1 Transmits Signal to the Nucleus / cytoplasmic vesicle membrane / skeletal system development / clathrin-coated endocytic vesicle membrane / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of protein phosphorylation / intracellular calcium ion homeostasis / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / endocytic vesicle membrane / Signaling by BRAF and RAF1 fusions / Vasopressin regulates renal water homeostasis via Aquaporins / Cargo recognition for clathrin-mediated endocytosis / protein transport / Clathrin-mediated endocytosis / Thrombin signalling through proteinase activated receptors (PARs) / cytoplasmic vesicle / basolateral plasma membrane / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / ubiquitin-dependent protein catabolic process / in utero embryonic development / molecular adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / transcription coactivator activity / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / receptor complex / cell population proliferation / apical plasma membrane / endosome / Ub-specific processing proteases / nuclear body / protein ubiquitination / G protein-coupled receptor signaling pathway / Golgi membrane / negative regulation of cell population proliferation / lysosomal membrane / positive regulation of cell population proliferation / ubiquitin protein ligase binding / positive regulation of gene expression / regulation of transcription by RNA polymerase II / chromatin / nucleolus / perinuclear region of cytoplasm / endoplasmic reticulum / Golgi apparatus
Similarity search - Function
Vasopressin V2 receptor / GPCR, family 2, parathyroid hormone receptor / Vasopressin receptor / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain ...Vasopressin V2 receptor / GPCR, family 2, parathyroid hormone receptor / Vasopressin receptor / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin-like, C-terminal / 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 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. / Immunoglobulin E-set
Similarity search - Domain/homology
Vasopressin V2 receptor / Beta-arrestin-1 / Parathyroid hormone/parathyroid hormone-related peptide receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsZhao, L. / Yuan, Q.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: To Be Published
Title: A Cryo-EM structure of LA-PTH-PTH1R-B-arrestin1 complex (state 1 conformation)
Authors: Zhao, L. / Yuan, Q.
History
DepositionFeb 19, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Mar 4, 2026Provider: repository / Type: Initial release
Revision 1.0Mar 4, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Mar 4, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 4, 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

Downloads & links

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Assembly

Deposited unit
B: Beta-arrestin-1
C: Fab30H
E: Fab30L
L: LA-PTH
R: Parathyroid hormone/parathyroid hormone-related peptide receptor,Vasopressin V2 receptor


Theoretical massNumber of molelcules
Total (without water)154,9675
Polymers154,9675
Non-polymers00
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 Beta-arrestin-1 / Arrestin beta-1 / Non-visual arrestin-2


Mass: 43995.246 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ARRB1, ARR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P49407
#2: Antibody Fab30H


Mass: 25551.494 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)
#3: Antibody Fab30L


Mass: 23244.842 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)
#4: Protein/peptide LA-PTH


Mass: 4274.027 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)
#5: Protein Parathyroid hormone/parathyroid hormone-related peptide receptor,Vasopressin V2 receptor / PTH/PTHrP type I receptor / PTH/PTHr receptor / Parathyroid hormone 1 receptor / PTH1 receptor / ...PTH/PTHrP type I receptor / PTH/PTHr receptor / Parathyroid hormone 1 receptor / PTH1 receptor / V2R / AVPR V2 / Antidiuretic hormone receptor / Renal-type arginine vasopressin receptor


Mass: 57901.793 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTH1R, PTHR, PTHR1, AVPR2, ADHR, DIR, DIR3, V2R / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q03431, UniProt: P30518
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: A Cryo-EM structure of LA-PTH-PTH1R-V2R-Beta-arrestin1 complex (state 1 conformation)
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.04
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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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: 18000 nm / Nominal defocus min: 8000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX1.20.1_4487model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 80488 / Symmetry type: POINT
RefinementHighest resolution: 3.1 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0019044
ELECTRON MICROSCOPYf_angle_d0.4612282
ELECTRON MICROSCOPYf_dihedral_angle_d9.5183265
ELECTRON MICROSCOPYf_chiral_restr0.0391393
ELECTRON MICROSCOPYf_plane_restr0.0031539

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