HELIX INITIATION AND ESTROGEN RECEPTOR-ALPHA ACTIVATION

描述：(改编自《调查者摘要》)：目标1是测试 螺旋12的替代起始基序调控假说 内质网的构象变化，从而调节功能。目标2将测试 假设Asp 351与螺旋12相互作用，从而稳定 活性构象。目标3将检验这样的假设，即对手 两种修饰的雌激素的活性是由于干扰了适当的 螺旋12的启动和/或对Asp 351之间相互作用的干扰 和螺旋12。拟议的研究将使用突变分析，配体 结合研究，圆二色谱，以及测量 蛋白质稳定性、反式激活能力以及与辅活化子的结合 和辅抑制物。

DESCRIPTION: (Adapted from the Investigator's Abstract): Aim 1 is to test the hypothesis that alternative initiation motifs for helix 12 regulate conformational changes in ER, and hence regulate function. Aim 2 will test the hypothesis that Asp 351 interacts with helix 12 and thereby stabilizes the active conformation. Aim 3 will test the hypothesis that the antagonist activity of two modified estrogens is due to interference with proper initiation of helix 12 and/or interference with the interaction between Asp 351 and helix 12. The proposed research will use mutational analysis, ligand binding studies, circular dichroism spectroscopy, as well as measurements of protein stability, transactivation ability, and association with coactivators and corepressors.