HELIX INITIATION AND ESTROGEN RECEPTOR-ALPHA ACTIVATION

Helix 启动和雌激素受体-α 激活

• 批准号: 6524463
• 负责人: DEBRA F SKAFAR
• 金额: $ 18.63万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524463
• 关键词: X ray crystallography; circular dichroism; conformation; estradiol; estrogen analog; estrogen receptors; hydrogen bond; ligands; nuclear receptors; protein structure function; receptor binding; site directed mutagenesis; tamoxifen

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.

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。

项目成果

Targeted mutation of key residues at the start of helix 12 in the hERalpha ligand-binding domain identifies the role of hydrogen-bonding and hydrophobic interactions in the activity of the protein.

hERα 配体结合结构域中螺旋 12 起始处的关键残基的靶向突变确定了氢键和疏水相互作用在蛋白质活性中的作用。

• DOI: 10.1016/j.jsbmb.2005.06.036
• 发表时间: 2006
• 期刊: The Journal of steroid biochemistry and molecular biology
• 作者: Zhao,Changqing;Abrams,Judith;Skafar,DebraF
• 通讯作者: Skafar,DebraF

Mutations of tyrosine 537 in the human estrogen receptor-alpha selectively alter the receptor's affinity for estradiol and the kinetics of the interaction.

人雌激素受体-α 中酪氨酸 537 的突变选择性地改变受体对雌二醇的亲和力以及相互作用的动力学。

• DOI: 10.1021/bi0121095
• 发表时间: 2002
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Zhong,L;Skafar,DF
• 通讯作者: Skafar,DF