Pissios P, Tzameli I, Kushner P, Moore D D
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Mol Cell. 2000 Aug;6(2):245-53. doi: 10.1016/s1097-2765(00)00026-5.
We have developed a novel assembly assay to examine structural changes in the ligand binding domain (LBD) of the thyroid hormone receptor (TR). Fragments including the first helix of the TR LBD interact only weakly with the remainder of the LBD in the absence of hormone, but this interaction is strongly enhanced by the addition of either hormone or the corepressor NCoR. Since neither the ligand nor the corepressor shows direct interaction with this helix, we propose that both exert their effects by stabilizing the overall structure of the LBD. Current models of activation of nuclear hormone receptors focus on a ligand-induced allosteric shift in the position of the C-terminal helix 12 that generates the coactivator binding site. Our results suggest that ligand binding also has more global effects that dynamically alter the structure of the receptor LBD.
我们开发了一种新型组装试验,以检测甲状腺激素受体(TR)配体结合域(LBD)的结构变化。在没有激素的情况下,包含TR LBD第一个螺旋的片段与LBD的其余部分相互作用较弱,但添加激素或共抑制因子NCoR后,这种相互作用会显著增强。由于配体和共抑制因子均未显示与该螺旋的直接相互作用,我们提出两者都是通过稳定LBD的整体结构来发挥作用的。目前核激素受体激活模型聚焦于配体诱导的C末端螺旋12位置的变构移位,从而产生共激活因子结合位点。我们的结果表明,配体结合还具有更广泛的作用,能动态改变受体LBD的结构。