Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA

Xiaohua Lou, Gudrun Toresson, Cindy Benod, Ji Ho Suh, Kevin J. Philips, Paul Webb, Jan Ake Gustafsson

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Nuclear receptors (NRs) are conditional transcription factors with common multidomain organization that bind diverse DNA elements. How DNA sequences influence NR conformation is poorly understood. Here we report the crystal structure of the human retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on its cognate element, an AGGTCA direct repeat spaced by 4 nt. The complex has an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed, in contrast to the parallel domain arrangement of other NRs that bind an AGGTCA direct repeat spaced by 1 nt. The LXRβ core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response element. Comparisons of RXRα-LXRβs in the crystal asymmetric unit and with previous NR structures reveal flexibility in NR organization and suggest a role for RXRα in adaptation of heterodimeric complexes to DNA.

Original languageEnglish (US)
Pages (from-to)277-281
Number of pages5
JournalNature Structural and Molecular Biology
Volume21
Issue number3
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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