Structure of the retinoid X receptor alpha-liver X receptor beta (RXR alpha-LXR beta) heterodimer on DNA

作者：Lou Xiaohua; Toresson Gudrun; Benod Cindy; Suh Ji Ho; Philips Kevin J; Webb Paul; Gustafsson Jan Ake^*

来源：Nature Structural & Molecular Biology, 2014, 21(3): 277-281.

DOI：10.1038/nsmb.2778

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 alpha-liver X receptor beta (RXR alpha-LXR beta) 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 LXR beta core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response element. Comparisons of RXR alpha-LXR beta s in the crystal asymmetric unit and with previous NR structures reveal flexibility in NR organization and suggest a role for RXRa in adaptation of heterodimeric complexes to DNA.

• 出版日期2014-3