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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism*
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Dimerization
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Humans
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Models, Molecular
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Protein Binding
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Protein Conformation
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Retinoic Acid / chemistry*
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Receptors, Retinoic Acid / metabolism
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Repressor Proteins / chemistry*
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Repressor Proteins / metabolism
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Transcription Factors / metabolism*
Substances
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DAX-1 Orphan Nuclear Receptor
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DNA-Binding Proteins
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NR0B1 protein, human
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NR5A2 protein, human
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Repressor Proteins
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Transcription Factors