3L2J

Dimeric structure of the ligand-free extracellular domain of the human parathyroid hormone receptor (PTH1R)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.24 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation.

Pioszak, A.A.Harikumar, K.G.Parker, N.R.Miller, L.J.Xu, H.E.

(2010) J Biol Chem 285: 12435-12444

  • DOI: https://doi.org/10.1074/jbc.M109.093138
  • Primary Citation of Related Structures:  
    3L2J

  • PubMed Abstract: 

    The parathyroid hormone receptor (PTH1R) is a class B G protein-coupled receptor that is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Little is known about the oligomeric state of the receptor and its regulation by hormone. The crystal structure of the ligand-free PTH1R extracellular domain (ECD) reveals an unexpected dimer in which the C-terminal segment of both ECD protomers forms an alpha-helix that mimics PTH/PTHrP by occupying the peptide binding groove of the opposing protomer. ECD-mediated oligomerization of intact PTH1R was confirmed in living cells by bioluminescence and fluorescence resonance energy transfer experiments. As predicted by the structure, PTH binding disrupted receptor oligomerization. A receptor rendered monomeric by mutations in the ECD retained wild-type PTH binding and cAMP signaling ability. Our results are consistent with the hypothesis that PTH1R forms constitutive dimers that are dissociated by ligand binding and that monomeric PTH1R is capable of activating G protein.


  • Organizational Affiliation

    Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA. augie.pioszak@vai.org


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fusion protein of Maltose-binding periplasmic protein and Parathyroid hormone/parathyroid hormone-related peptide receptor
A, B
535Escherichia coli K-12Homo sapiens
This entity is chimeric
Mutation(s): 0 
Gene Names: b4034JW3994malEPTHR1
UniProt & NIH Common Fund Data Resources
Find proteins for P0AEX9 (Escherichia coli (strain K12))
Explore P0AEX9 
Go to UniProtKB:  P0AEX9
Find proteins for Q03431 (Homo sapiens)
Explore Q03431 
Go to UniProtKB:  Q03431
PHAROS:  Q03431
GTEx:  ENSG00000160801 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP0AEX9Q03431
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose
C, D
2N/A
Glycosylation Resources
GlyTouCan:  G07411ON
GlyCosmos:  G07411ON
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.24 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 136.702α = 90
b = 182.326β = 90
c = 97.166γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-02-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-08-02
    Changes: Refinement description, Source and taxonomy
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2023-09-06
    Changes: Data collection, Database references, Refinement description, Structure summary