The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1.
The Dax-1 protein is an enigmatic nuclear receptor that lacks an expected DNA binding domain, yet functions as a potent corepressor of nuclear receptors. Here we report the structure of Dax-1 bound to one of its targets, liver receptor homolog 1 (LRH-1). Unexpectedly, Dax-1 binds to LRH-1 using a new module, a repressor helix built from a family conserved sequence motif, PCFXXLP. Mutations in this repressor helix that are linked with human endocrine disorders dissociate the complex and attenuate Dax-1 function. The structure of the Dax-1:LRH-1 complex provides the molecular mechanism for the function of Dax-1 as a potent transcriptional repressor.
Sablin
Elena P
EP
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Woods
April
A
Krylova
Irina N
IN
Hwang
Peter
P
Ingraham
Holly A
HA
Fletterick
Robert J
RJ
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors