Functional characterization of splicing and ligand-binding domain variants in the LDL receptor

2011 ◽  
Vol 33 (1) ◽  
pp. 232-243 ◽  
Author(s):  
Aitor Etxebarria ◽  
Lourdes Palacios ◽  
Marianne Stef ◽  
Diego Tejedor ◽  
Kepa B. Uribe ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Functional Characterization ◽  
Ldl Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain

Refolding and characterization of the functional ligand-binding domain of human lectin-like oxidized LDL receptor

2003 ◽  
Vol 32 (1) ◽  
pp. 68-74 ◽  
Author(s):  
Qiuhong Xie ◽  
Shigeru Matsunaga ◽  
Xiaohua Shi ◽  
Setsuko Ogawa ◽  
Setsuko Niimi ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Oxidized Ldl ◽  
Ldl Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain

scholarly journals Characterization of the Nurr1 ligand-binding domain co-activator interaction surface

2006 ◽  
Vol 37 (2) ◽  
pp. 317-326 ◽  
Author(s):  
Nikolaos Volakakis ◽  
Michal Malewicz ◽  
Banafsheh Kadkhodai ◽  
Thomas Perlmann ◽  
Gerard Benoit
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Close Association ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Site Directed Mutagenesis ◽  
Orphan Nuclear Receptor ◽  
Hydrophobic Region ◽  
Binding Surface

The recently solved crystal structure of the orphan nuclear receptor (NR) Nurr1 ligand-binding domain (LBD) showed that Nurr1 lacks a cavity for ligand binding and a canonical NR co-activator-binding site. Computer modeling of the Nurr1 LBD structure identified a hydrophobic region on the surface of the Nurr1 LBD that was positioned on the opposite side from the classical co-activator-binding site. Site-directed mutagenesis demonstrated that this region is critical for the activity of the Nurr1 LBD. Most mutations introduced in this region reduced or abolished transcriptional activity of the Nurr1 LBD, but mutation at lysine (K577) resulted in a drastically increased activity. Moreover, the activity of the Nurr1 LBD was shown to correlate with a propensity for proteasome-dependent degradation revealing a close association between activity and Nurr1 protein turnover. These data provide novel insights into the mechanisms of transcription via the Nurr1 LBD and identify an alternative co-activator-binding surface that is unique to the NR4A family of NRs.

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