4BVA

Crystal structure of the NADPH-T3 form of mouse Mu-crystallin.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.146 
  • R-Value Observed: 0.149 

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This is version 2.1 of the entry. See complete history


Literature

Crystal Structure of Mouse Mu-Crystallin Complexed with Nadph and the T3 Thyroid Hormone

Borel, F.Hachi, I.Palencia, A.Gaillard, M.C.Ferrer, J.L.

(2014) FEBS J 281: 1598

  • DOI: https://doi.org/10.1111/febs.12726
  • Primary Citation of Related Structures:  
    4BV8, 4BV9, 4BVA

  • PubMed Abstract: 

    Mu-crystallin (CRYM), first described as a structural component of the eye lens in marsupials, has been characterized as an NADPH-dependent cytosolic T3 thyroid hormone (triiodothyronine) binding protein. More recently, CRYM has also been associated with ketimine reductase activity. Here, we report three crystal structures: mouse CRYM (mCRYM) in its apo form, in a form complexed with NADPH, and in a form with both NADPH and triiodothyronine bound. Comparison of the apo and NADPH forms reveals a rearrangement of the protein upon NADPH binding that reduces the degrees of freedom of several residues and traps the conformation of the binding pocket in a more T3 competent state. These findings are in agreement with the cooperative mechanism identified using isothermal titration calorimetry. Our structure with T3 reveals for the first time the location of the hormone binding site and shows its detailed interactions. T3 binding involves mainly hydrophobic interactions. Only five residues, either directly or through bridging water molecules, are hydrogen bonded to the hormone. Using in silico docking analysis, a series of ring-containing hydrophobic molecules were identified as potential mCRYM ligands, suggesting that the specificity for the recognition of the hydrophobic part of the hormone might be low. This is in agreement with the ketimine reductase activity that has been identified for ovine CRYM, as it demonstrates how a protein known as a thyroid hormone transporter can accommodate the ringed molecules required for its ketimine reductase activity. In the light of our results, a putative role of CRYM in thyroid hormone metabolism is also discussed.


  • Organizational Affiliation

    Institut de Biologie Structurale, Université de Grenoble Alpes, CEA, CNRS, France.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
THIOMORPHOLINE-CARBOXYLATE DEHYDROGENASE
A, B
335Mus musculusMutation(s): 0 
EC: 1.5.1.25
UniProt
Find proteins for O54983 (Mus musculus)
Explore O54983 
Go to UniProtKB:  O54983
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO54983
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.146 
  • R-Value Observed: 0.149 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.24α = 90
b = 97.14β = 104.9
c = 75.67γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-02-05
    Type: Initial release
  • Version 1.1: 2014-04-02
    Changes: Database references
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations, Other
  • Version 2.1: 2023-12-20
    Changes: Refinement description