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Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18390-5. doi: 10.1073/pnas.0808936105. Epub 2008 Nov 17.

The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1.

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  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.


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.

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