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PDBsum entry 4iv4

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protein ligands Protein-protein interface(s) links
Transcription PDB id
4iv4
Jmol PyMol
Contents
Protein chains
229 a.a.
232 a.a.
Ligands
HIS-LYS-ILE-LEU-
HIS-ARG-LEU-LEU-
GLN-ASP
LYS-ILE-LEU-HIS-
ARG-LEU-LEU-GLN-
ASP
1GS ×2
Waters ×112
PDB id:
4iv4
Name: Transcription
Title: Crystal structure of the estrogen receptor alpha ligand-bind in complex with constrained way-derivative, 5b
Structure: Estrogen receptor. Chain: a, b. Fragment: ligand-binding domain, unp residues 303-549. Synonym: er, er-alpha, estradiol receptor, nuclear receptor 3 group a member 1. Engineered: yes. Mutation: yes. Nuclear receptor coactivator 2. Chain: c, d.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: esr, esr1, nr3a1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans
Resolution:
2.30Å     R-factor:   0.197     R-free:   0.237
Authors: J.C.Nwachukwu,S.Srinivasan,A.A.Parent,V.Cavett,J.Nowak,T.S.H D.J.Kojetin,J.A.Katzenellenbogen,K.W.Nettles
Key ref: S.Srinivasan et al. (2013). Ligand-binding dynamics rewire cellular signaling via estrogen receptor-α. Nat Chem Biol, 9, 326-332. PubMed id: 23524984 DOI: 10.1038/nchembio.1214
Date:
22-Jan-13     Release date:   27-Mar-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03372  (ESR1_HUMAN) -  Estrogen receptor
Seq:
Struc:
 
Seq:
Struc:
595 a.a.
229 a.a.*
Protein chain
Pfam   ArchSchema ?
P03372  (ESR1_HUMAN) -  Estrogen receptor
Seq:
Struc:
 
Seq:
Struc:
595 a.a.
232 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 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     2 terms  

 

 
DOI no: 10.1038/nchembio.1214 Nat Chem Biol 9:326-332 (2013)
PubMed id: 23524984  
 
 
Ligand-binding dynamics rewire cellular signaling via estrogen receptor-α.
S.Srinivasan, J.C.Nwachukwu, A.A.Parent, V.Cavett, J.Nowak, T.S.Hughes, D.J.Kojetin, J.A.Katzenellenbogen, K.W.Nettles.
 
  ABSTRACT  
 
Ligand-binding dynamics control allosteric signaling through the estrogen receptor-α (ERα), but the biological consequences of such dynamic binding orientations are unknown. Here, we compare a set of ER ligands having dynamic binding orientation (dynamic ligands) with a control set of isomers that are constrained to bind in a single orientation (constrained ligands). Proliferation of breast cancer cells directed by constrained ligands is associated with DNA binding, coactivator recruitment and activation of the estrogen-induced gene GREB1, reflecting a highly interconnected signaling network. In contrast, proliferation driven by dynamic ligands is associated with induction of ERα-mediated transcription in a DNA-binding domain (DBD)-dependent manner. Further, dynamic ligands showed enhanced anti-inflammatory activity. The DBD-dependent profile was predictive of these signaling patterns in a larger diverse set of natural and synthetic ligands. Thus, ligand dynamics directs unique signaling pathways and reveals a new role of the DBD in allosteric control of ERα-mediated signaling.
 

 

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