Spanjaard R A, Darling D S, Chin W W
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8587-91. doi: 10.1073/pnas.88.19.8587.
The ligand-binding domain of the thyroid hormone (3,5,3'-triiodothyronine) receptor (TR) contains poorly characterized subdomains involved with ligand binding, transactivation, and protein-protein interactions. The region between residues 288-331 of rat TR alpha-1 was analyzed by modeling and site-directed mutagenesis. Our results suggest that part of this sequence adopts an amphipathic alpha-helical conformation. The integrity of the putative helix is important for 3,5,3'-triiodothyronine binding but not necessarily for heterodimerization with nuclear factor(s). Mutants defective for both activities were found clustered in a region overlapping the C-terminal portion of the helix and further downstream. The sequence conservation of this particular region among the entire superfamily suggests a similar role in dimerization in other receptors.
甲状腺激素（3,5,3'-三碘甲腺原氨酸）受体（TR）的配体结合结构域包含与配体结合、反式激活和蛋白质-蛋白质相互作用相关但特征不明的亚结构域。通过建模和定点诱变分析了大鼠TRα-1第288 - 331位残基之间的区域。我们的结果表明，该序列的一部分呈现两亲性α-螺旋构象。推定螺旋的完整性对于3,5,3'-三碘甲腺原氨酸的结合很重要，但对于与核因子的异源二聚化不一定重要。发现两种活性均有缺陷的突变体聚集在与螺旋C末端部分重叠且更下游的区域。在整个超家族中该特定区域的序列保守性表明其在其他受体的二聚化中起类似作用。
