1ovl
From Proteopedia
|
Crystal Structure of Nurr1 LBD
Contents |
Overview
Members of the nuclear receptor (NR) superfamily of transcription factors, modulate gene transcription in response to small lipophilic molecules., Transcriptional activity is regulated by ligands binding to the, carboxy-terminal ligand-binding domains (LBDs) of cognate NRs. A subgroup, of NRs referred to as 'orphan receptors' lack identified ligands, however, raising issues about the function of their LBDs. Here we report the, crystal structure of the LBD of the orphan receptor Nurr1 at 2.2 A, resolution. The Nurr1 LBD adopts a canonical protein fold resembling that, of agonist-bound, transcriptionally active LBDs in NRs, but the structure, has two distinctive features. First, the Nurr1 LBD contains no cavity as a, result of the tight packing of side chains from several bulky hydrophobic, residues in the region normally occupied by ligands. Second, Nurr1 lacks a, 'classical' binding site for coactivators. Despite these differences, the, Nurr1 LBD can be regulated in mammalian cells. Notably, transcriptional, activity is correlated with the Nurr1 LBD adopting a more stable, conformation. Our findings highlight a unique structural class of NRs and, define a model for ligand-independent NR function.
Disease
Known diseases associated with this structure: Parkinson disease OMIM:[601828]
About this Structure
1OVL is a Protein complex structure of sequences from Homo sapiens with K, BR and IOD as ligands. Full crystallographic information is available from OCA.
Reference
Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors., Wang Z, Benoit G, Liu J, Prasad S, Aarnisalo P, Liu X, Xu H, Walker NP, Perlmann T, Nature. 2003 May 29;423(6939):555-60. PMID:12774125
Page seeded by OCA on Mon Nov 12 18:37:06 2007
Categories: Homo sapiens | Protein complex | Liu, J. | Walker, N. | Wang, Z. | BR | IOD | K | Lbd | Nuur1
