The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1
- 25 November 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (47), 18390-18395
- https://doi.org/10.1073/pnas.0808936105
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.Keywords
This publication has 55 references indexed in Scilit:
- A protein interaction network for pluripotency of embryonic stem cellsNature, 2006
- Analysis of DAX1 (NR0B1) and Steroidogenic Factor-1 (NR5A1) in Children and Adults with Primary Adrenal Failure: Ten Years’ ExperienceJournal of Clinical Endocrinology & Metabolism, 2006
- Crystal Structure of the Human LRH-1 DBD–DNA Complex Reveals Ftz-F1 Domain Positioning is Required for Receptor ActivityJournal of Molecular Biology, 2005
- Activation of the p38 MAPK pathway by follicle-stimulating hormone regulates steroidogenesis in granulosa cells differentiallyJournal of Endocrinology, 2005
- Transcriptional regulation of aromatase in placenta and ovaryThe Journal of Steroid Biochemistry and Molecular Biology, 2005
- Inhibition of Androgen Receptor (AR) Function by the Reproductive Orphan Nuclear Receptor DAX-1Molecular Endocrinology, 2002
- DAX-1 Functions as an LXXLL-containing Corepressor for Activated Estrogen ReceptorsJournal of Biological Chemistry, 2000
- Interaction of the Corepressor Alien with DAX-1 Is Abrogated by Mutations of DAX-1 Involved in Adrenal Hypoplasia CongenitaPublished by Elsevier BV ,2000
- Structure and specificity of nuclear receptor–coactivator interactionsGenes & Development, 1998
- An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenitaNature, 1994