A structural model of the constitutive androstane receptor defines novel interactions that mediate ligand-independent activity.

ABSTRACT: Unlike classical nuclear receptors that require ligand for transcriptional activity, the constitutive androstane receptor (CAR) is active in the absence of ligand. To determine the molecular contacts that underlie this constitutive activity, we created a three-dimensional model of CAR and verified critical structural features by mutational analysis. We found that the same motifs that facilitate ligand-dependent activity in classical receptors also mediated constitutive activity in CAR. This raises a critical question: how are these motifs maintained in an active conformation in unliganded CAR? The model identified several novel interactions that account for this activity. First, CAR possesses a short loop between helix 11 and the transactivation domain (helix 12), as well as a short carbox

SUBMITTER: Dussault I 

PROVIDER: S-EPMC133936 | biostudies-literature | 2002 Aug

REPOSITORIES: biostudies-literature