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PDBsum entry 1y0x

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protein ligands links
Hormone/growth factor receptor PDB id
1y0x
Jmol
Contents
Protein chain
250 a.a. *
Ligands
CAC ×6
T44
Waters ×10
* Residue conservation analysis
PDB id:
1y0x
Name: Hormone/growth factor receptor
Title: Thyroxine-thyroid hormone receptor interactions
Structure: Thyroid hormone receptor beta-1. Chain: x. Fragment: ligand binding domain (residues 202-461). Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: thrb, erba2, nr1a2, thr1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
3.10Å     R-factor:   0.225     R-free:   0.266
Authors: B.Sandler,P.Webb,J.W.Apriletti,B.R.Huber,M.Togashi,S.T.Cunha S.Juric,S.Nilsson,R.Wagner,R.J.Fletterick,J.D.Baxter
Key ref:
B.Sandler et al. (2004). Thyroxine-thyroid hormone receptor interactions. J Biol Chem, 279, 55801-55808. PubMed id: 15466465 DOI: 10.1074/jbc.M410124200
Date:
16-Nov-04     Release date:   07-Dec-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10828  (THB_HUMAN) -  Thyroid hormone receptor beta
Seq:
Struc:
461 a.a.
250 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  

 

 
DOI no: 10.1074/jbc.M410124200 J Biol Chem 279:55801-55808 (2004)
PubMed id: 15466465  
 
 
Thyroxine-thyroid hormone receptor interactions.
B.Sandler, P.Webb, J.W.Apriletti, B.R.Huber, M.Togashi, S.T.Cunha Lima, S.Juric, S.Nilsson, R.Wagner, R.J.Fletterick, J.D.Baxter.
 
  ABSTRACT  
 
Thyroid hormone (TH) actions are mediated by nuclear receptors (TRs alpha and beta) that bind triiodothyronine (T(3), 3,5,3'-triiodo-l-thyronine) with high affinity, and its precursor thyroxine (T(4), 3,5,3',5'-tetraiodo-l-thyronine) with lower affinity. T(4) contains a bulky 5' iodine group absent from T(3). Because T(3) is buried in the core of the ligand binding domain (LBD), we have predicted that TH analogues with 5' substituents should fit poorly into the ligand binding pocket and perhaps behave as antagonists. We therefore examined how T(4) affects TR activity and conformation. We obtained several lines of evidence (ligand dissociation kinetics, migration on hydrophobic interaction columns, and non-denaturing gels) that TR-T(4) complexes adopt a conformation that differs from TR-T(3) complexes in solution. Nonetheless, T(4) behaves as an agonist in vitro (in effects on coregulator and DNA binding) and in cells, when conversion to T(3) does not contribute to agonist activity. We determined x-ray crystal structures of the TRbeta LBD in complex with T(3) and T(4) at 2.5-A and 3.1-A resolution. Comparison of the structures reveals that TRbeta accommodates T(4) through subtle alterations in the loop connecting helices 11 and 12 and amino acid side chains in the pocket, which, together, enlarge a niche that permits helix 12 to pack over the 5' iodine and complete the coactivator binding surface. While T(3) is the major active TH, our results suggest that T(4) could activate nuclear TRs at appropriate concentrations. The ability of TR to adapt to the 5' extension should be considered in TR ligand design.
 
  Selected figure(s)  
 
Figure 3.
FIG. 3. T[4] acts as an agonist in vitro. A, autoradiograms of SDS-polyacrylamide gels, showing the amount of radiolabeled TR retained on columns containing bacterially expressed nuclear receptor-interacting fragments of GRIP1 and TRAP220. B, as in A, except that the NR-interacting region of the corepressor N-CoR is used as bait for TR.
Figure 6.
FIG. 6. Structure of the TR -T[4] complex. Superimposed ribbon diagrams of TR -T[3] complex (cyan) and the TR -T[4] complex (pink) show that the overall fold is nearly identical. The coactivator binding surface H3, 4, 5, and 12 is labeled.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 55801-55808) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21336335 P.Metrangolo, and G.Resnati (2011).
Tracing iodine.
  Nat Chem, 3, 260.  
21184528 S.Kim, K.Ji, S.Lee, J.Lee, J.Kim, S.Kim, Y.Kho, and K.Choi (2011).
Perfluorooctane sulfonic acid exposure increases cadmium toxicity in early life stage of zebrafish, Danio rerio.
  Environ Toxicol Chem, 30, 870-877.  
19926848 L.Martínez, A.S.Nascimento, F.M.Nunes, K.Phillips, R.Aparicio, S.M.Dias, A.C.Figueira, J.H.Lin, P.Nguyen, J.W.Apriletti, F.A.Neves, J.D.Baxter, P.Webb, M.S.Skaf, and I.Polikarpov (2009).
Gaining ligand selectivity in thyroid hormone receptors via entropy.
  Proc Natl Acad Sci U S A, 106, 20717-20722.
PDB codes: 3jzb 3jzc
19725882 S.J.Richardson (2009).
Evolutionary changes to transthyretin: evolution of transthyretin biosynthesis.
  FEBS J, 276, 5342-5356.  
19729063 S.T.Cunha Lima, N.H.Nguyen, M.Togashi, J.W.Apriletti, P.Nguyen, I.Polikarpov, T.S.Scanlan, J.D.Baxter, and P.Webb (2009).
Differential effects of TR ligands on hormone dissociation rates: evidence for multiple ligand entry/exit pathways.
  J Steroid Biochem Mol Biol, 117, 125-131.  
18558711 M.Jeyakumar, P.Webb, J.D.Baxter, T.S.Scanlan, and J.A.Katzenellenbogen (2008).
Quantification of ligand-regulated nuclear receptor corepressor and coactivator binding, key interactions determining ligand potency and efficacy for the thyroid hormone receptor.
  Biochemistry, 47, 7465-7476.  
18550270 S.J.Richardson (2008).
Marsupial models for understanding evolution of thyroid hormone distributor proteins.
  Mol Cell Endocrinol, 293, 32-42.  
15980170 L.Martínez, M.T.Sonoda, P.Webb, J.D.Baxter, M.S.Skaf, and I.Polikarpov (2005).
Molecular dynamics simulations reveal multiple pathways of ligand dissociation from thyroid hormone receptors.
  Biophys J, 89, 2011-2023.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.