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PDBsum entry 1nuo

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Hormone/growth factor receptor PDB id
1nuo
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Contents
Protein chain
247 a.a. *
Ligands
4HY
* Residue conservation analysis
PDB id:
1nuo
Name: Hormone/growth factor receptor
Title: Two rth mutants with impaired hormone binding
Structure: Thyroid hormone receptor beta-1. Chain: a. Fragment: ligand binding domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: thrb or nr1a2 or erba2 or thr1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
3.10Å     R-factor:   0.257     R-free:   0.302
Authors: B.R.Huber,B.Sandler,B.L.West,S.T.Cunha-Lima,H.T.Nguyen, J.W.Apriletti,J.D.Baxter,R.J.Fletterick
Key ref: B.R.Huber et al. (2003). Two resistance to thyroid hormone mutants with impaired hormone binding. Mol Endocrinol, 17, 643-652. PubMed id: 12554782
Date:
31-Jan-03     Release date:   15-Apr-03    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10828  (THB_HUMAN) -  Thyroid hormone receptor beta
Seq:
Struc:
461 a.a.
247 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     3 terms  

 

 
Mol Endocrinol 17:643-652 (2003)
PubMed id: 12554782  
 
 
Two resistance to thyroid hormone mutants with impaired hormone binding.
B.R.Huber, B.Sandler, B.L.West, S.T.Cunha Lima, H.T.Nguyen, J.W.Apriletti, J.D.Baxter, R.J.Fletterick.
 
  ABSTRACT  
 
Resistance to hormones is commonly due to mutations in genes encoding receptors. Resistance to thyroid hormone is due mostly to mutations of the beta-form of the human (h) thyroid hormone receptor (hTRbeta). We determined x-ray crystal structures of two hTRbeta ligand-binding domains (LBDs), Ala 317 Thr and Arg 316 His. Amino acids 316 and 317 form part of the hormone-binding pocket. The methyl of Ala 317, contacting iodine, sculpts the T3 hormone-binding pocket. Arg 316 is not in direct contact with T3 and has an unknown role in function. Remarkably, the Arg forms part of an unusual buried polar cluster in hTRbeta. Although the identity of the amino acids changes, the polar cluster appears in all nuclear receptors. In spite of the differing roles of 316 and 317, both resistance to thyroid hormone mutants display decreased T3 affinity and weakened transcriptional activation. The two mutants differ in that the Arg 316 His receptor does not form TR-TR homodimers on DNA. 3,5,3'-Triiodothyroacetic acid is bound to both receptors. Thr 317 repositions 3,5,3'-triiodothyroacetic acid distending the face of the receptor that binds coregulators. Arg 316 forms two hydrogen bonds with helix 1. Both are lost with mutation to His displacing helix 1 of the LBD and disordering the loop after helix 1. The stability of the helix 1, deriving in part from the buried polar cluster, is important for hormone binding and formation of TR dimers. The observation that the Arg 316 His mutation affects these functions implies a role for helix 1 in linking hormone binding to the DNA-binding domain-LBD configuration.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
14673100 S.Borngraeber, M.J.Budny, G.Chiellini, S.T.Cunha-Lima, M.Togashi, P.Webb, J.D.Baxter, T.S.Scanlan, and R.J.Fletterick (2003).
Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor.
  Proc Natl Acad Sci U S A, 100, 15358-15363.
PDB code: 1q4x
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 code is shown on the right.

 

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