MUTATION ANALYSIS OF THYROID RECEPTOR FUNCTION

描述（改编自申请人摘要）：在拟定的 研究中，研究人员计划利用结构信息 准备一个特定突变库， 改变TR LBD表面，使得与其他蛋白质的相互作用 参与各种TR功能的细胞可能会受到干扰。还计划 来制备突变， 被称为tau-3和tau-4，被认为参与TR LBD转录 激活功能和可能涉及的HSP 70区域（HSP 70 -1） 各种TR功能。突变分子的活性将 通过T3结合（TR + T3）与DNA的结合试验和其他 蛋白质，并通过将表达突变TR的基因沿着 报告基因和表达其他蛋白质的基因 与哺乳动物细胞中的TRs结合。

DESCRIPTION (Adapted from the applicant's abstract): In the proposed studies, the investigators plan to utilized the structural information to prepare a library of specific mutations designed to systematically alter the TR LBD surface such that interactions with other proteins involved in various TR functions might be disrupted. It is also planned to prepare mutations that should influence the function of two regions termed tau-3 and tau-4 thought to be involved in TR LBD transcriptional activation functions and of a Helix region (Helix-1) that maybe involved in various TR functions. Activities of mutated molecules will be examined through assays of T3 binding (TR + T3) binding to DNA and other proteins and by transfecting genes that express the mutated TRs along with reporter genes and genes that express other proteins that interact with TRs in mammalian cells.