MUTATION ANALYSIS OF THYROID RECEPTOR FUNCTION

说明(改编自申请人的摘要)：在建议的 研究中，研究人员计划利用结构信息 准备一个特定突变的文库，旨在系统地 改变TRLBD表面，使其与其他蛋白质相互作用 参与各种tr功能的可能会中断。它也在计划中 准备应该影响两个区域功能的突变 被称为tau-3和tau-4的基因被认为与TRLBD转录有关 激活功能和可能涉及的螺旋区(Helix-1) 在各种tr功能中。突变分子的活性将是 通过T_3结合(TR+T_3)与DNA和其他 通过将表达突变的TRs的基因 带有报告基因和表达其他相互作用的蛋白质的基因 与哺乳动物细胞中的酪氨酸受体结合。

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.