Osz Judit, McEwen Alastair G, Poussin-Courmontagne Pierre, Moutier Emmanuel, Birck Catherine, Davidson Irwin, Moras Dino, Rochel Natacha
Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM) U964/Centre National de la Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, 67404 Illkirch, France.
Structural Biology Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM) U964/Centre National de la Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, 67404 Illkirch, France.
Sci Rep. 2015 Feb 3;5:8216. doi: 10.1038/srep08216.
Retinoid X receptors (RXRs) act as homodimers or heterodimerisation partners of class II nuclear receptors. RXR homo- and heterodimers bind direct repeats of the half-site (A/G)G(G/T)TCA separated by 1 nucleotide (DR1). We present a structural characterization of RXR-DNA binding domain (DBD) homodimers on several natural DR1s and an idealized symmetric DR1. Homodimers displayed asymmetric binding, with critical high-affinity interactions accounting for the 3' positioning of RXR in heterodimers on DR1s. Differing half-site and spacer DNA sequence induce changes in RXR-DBD homodimer conformation notably in the dimerization interface such that natural DR1s are bound with higher affinity than an idealized symmetric DR1. Subtle changes in the consensus DR1 DNA sequence therefore specify binding affinity through altered RXR-DBD-DNA contacts and changes in DBD conformation suggesting a general model whereby preferential half-site recognition determines polarity of heterodimer binding to response elements.
维甲酸X受体（RXRs）作为II类核受体的同型二聚体或异源二聚体结合伙伴发挥作用。RXR同型和异型二聚体结合由1个核苷酸分隔的半位点（A/G）G（G/T）TCA的直接重复序列（DR1）。我们展示了RXR-DNA结合结构域（DBD）同型二聚体在几个天然DR1和一个理想化对称DR1上的结构特征。同型二聚体表现出不对称结合，关键的高亲和力相互作用决定了RXR在DR1上异型二聚体中的3'定位。不同的半位点和间隔区DNA序列会诱导RXR-DBD同型二聚体构象发生变化，尤其是在二聚化界面，使得天然DR1的结合亲和力高于理想化对称DR1。因此，共有DR1 DNA序列中的细微变化通过改变RXR-DBD-DNA接触和DBD构象来确定结合亲和力，这提示了一个通用模型，即优先的半位点识别决定异型二聚体与反应元件结合的极性。
