Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA
Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA
复制标题
DOI：
10.1038/nsmb.2778
复制
发表时间：
2014-03-01
影响因子：
16.8
通讯作者：
Gustafsson, Jan-Ake
中科院分区：
文献类型：
--
作者：
Lou, Xiaohua;Toresson, Gudrun;Gustafsson, Jan-Ake
核受体是具有共同多结构域结构的条件转录因子，可结合多种DNA元件。DNA序列如何影响NR构象尚不清楚。在这里，我们报道了人类类视黄醇X受体α -肝脏X受体β (RXR α - lxr β)异源二聚体在其同源元件上的晶体结构，AGGTCA直接重复序列间隔为4 nt。该复合物具有扩展的X形排列，DNA和配体结合域交叉。与其他与AGGTCA直接重复序列间隔为1 nt的rna的平行结构域排列相反，LXR β核通过规范接触和辅助DNA接触结合DNA，从而增强对响应元件的亲和力。RXR α - lxr β s在晶体不对称单元和之前的NR结构的比较揭示了NR组织的灵活性，并提示RXRa在异二聚体复合物对DNA的适应中起作用。
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.