Structural Characterization of the Interdomain Features of the Estrogen Receptor
Abstract
The nuclear hormone receptor (NR) superfamily consists of 48 distinct transcription factors in humans. These proteins generally consist of inter-connected functional domains. The Nterminal A/B domain is poorly conserved in size and sequence. The DNA-binding domain (DBD) resides in the center of the polypeptide and binds to DNA response elements upstream of target genes. A hinge region connects the DBD to the ligand binding domain (LBD). The LBD is responsible for binding to the receptor ligand and to some coregulator proteins. There are no three-dimensional structures available for any intact nuclear receptors, or of an A/B domain or hinge region. By contrast, the isolated DBDs and LBDs have been studies by X-ray crystallography in many cases. In the case of the estrogen receptor (ER)-alpha, crystals structures are available for the LBD and DBD as single domains. Since structures consisting of intact or nearly intact polypeptides are entirely absent for this protein family, there is no conceptual framework to help understand their domain-domain interactions. We have therefore undertaken studies to crystallize full-length nuclear receptors including the ER-alpha, and at the same time of PPAR-gamma/RXR-alpha, in several different protein and DNA complexes. Our recent structure determination of the PPAR-gamma/ RXR-alpha heterodimer on DNA have revealed important new biological insights for the nuclear receptor family as a whole, including the estrogen receptor sub-family. We are currently employing several approaches are to help produce a similar crystal structure for ER.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA481193
Entities
People
- Fraydoon Rastinejad
Organizations
- University of Virginia