THYROID HORMONE INTERACTIONS WITH CELLS AND PROTEINS

甲状腺激素与细胞和蛋白质的相互作用

• 批准号: 3754843
• 负责人: J ROBBINS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3754843
• 关键词: apolipoproteins; chemical kinetics; chymotrypsin; corticosteroid binding protein; high density lipoproteins; hormone regulation /control mechanism; human tissue; intermolecular interaction; thyroid hormone binding protein; thyroid hormones; thyroxine

Drs. Benvenga and Robbins have continued efforts to understand the biochemical basis of thyroid hormone interaction with serum lipoproteins. The T4 binding domains of the HDL apolipoproteins have common features, including one site per molecule, affinity between serum albumin (HSA) and transthyretin (TTR); relative affinities for T4 analogs similar to HSA; distinct from the lipid the cell surface receptor binding domains; N- Terminal location. We previously reported sequence homology between the T4 binding domains of apoA-I, apoE and apoB-100 and have now extended this to other HDL apos, HSA, TTR and TBG using University of Wisconsin Genetics Computer Group and GenePro version 5 programs. Of 10 apo sequences, 5 or more had identical or conserved amino acids in 24/49 positions. The most conserved region was N-terminal in positions 1-26. A conserved motif (Y, L/I/V/M, X, X, V/L/I) occupied positions 22-26. There were 15-16 conserved residues homologous to the apos in HSA, but only 9-11 in TTR and TBG (a 50% difference). A 25 a.a. stretch of HSA, was >40% homologous with the apos. Thus we have shown that there is extensive homology between T4 binding domains even in distantly related proteins. Potential physiological importance of the thyroid hormone lipoprotein interactions have been discussed in an invited review in Trends in Endocrinology and Metabolism. Our previous work demonstrated that binding to LDL facilitated the entry of thyroxine into human fibroblasts and was mediated by the apoB/apoE cell surface receptor. Experiments are in progress to extend these observations to human hepatocytes and also to determine whether the lipoproteins are involved in the exit of thyroid hormone from the cells.

本文加博士和罗宾斯博士一直在努力了解 甲状腺激素与血清脂蛋白相互作用的生化基础。 高密度脂蛋白的T4结合区有共同的特征， 包括每个分子一个位点，血清白蛋白(HSA)和 转甲状腺素(TTR)；与HSA类似的T4类似物的相对亲和力； 与脂质不同的是细胞表面受体结合域；N- 终点站位置。我们之前报道了这两个基因之间的序列同源性 ApoA-I、apoE和apoB-100的T4结合结构域，现在已经扩展 使用威斯康星大学的其他高密度脂蛋白载脂蛋白、人血清白蛋白、总蛋白和总胆红素 遗传学计算机组和GenePro版本5程序。共10个载脂蛋白 24/49中有5个或更多氨基酸相同或保守的序列 各就各位。最保守的区域是1-26位的N-末端。 一个保守的基序(Y，L/I/V/M，X，X，V/L/I)占据第22-26位。 HSA中有15-16个与载脂蛋白同源的保守残基，但 TTR和TBG只有9-11(50%的差异)。25年前。一段血清白蛋白， 与载脂蛋白有40%的同源性。因此，我们已经证明，存在 T4结合域之间的广泛同源性，即使在远缘关系中 蛋白质。 甲状腺激素脂蛋白的潜在生理意义 互动已在《趋势》杂志的特邀评论中进行了讨论 内分泌学和新陈代谢。我们之前的工作证明了 与低密度脂蛋白结合促进甲状腺激素进入人成纤维细胞 并由apoB/apoE细胞表面受体介导。实验是 将这些观察扩展到人类肝细胞的研究进展中 以确定脂蛋白是否参与了甲状腺的退出 细胞中的荷尔蒙。