The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1.
basic_science · Level V
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- Record sourced from PubMed, PMID 19015525.
- Also identified by DOI 10.1073/pnas.0808936105 and PMC identifier 2587556.
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Abstract
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.
Medical subject headings
- DNA-Binding Proteins
- Receptors, Cytoplasmic and Nuclear
- Receptors, Retinoic Acid
- Repressor Proteins
- Transcription Factors