THYROID HORMONE INTERACTIONS WITH CELLS AND PROTEINS

本文加和罗宾斯博士继续努力了解 甲状腺激素与血清脂蛋白相互作用的生化基础。 HDL载脂蛋白的T4结合结构域具有共同的特征， 包括每个分子一个位点，血清白蛋白（HSA）和 甲状腺素运载蛋白（TTR）;与HSA相似的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结构域; N- 终点站位置。 我们先前报道了这些基因之间的序列同源性。 apoA-I、apoE和apoB-100的T4结合结构域，现已延伸至 这与其他HDL '，HSA，TTR和TBG使用威斯康星州大学 Genetics Computer Group和GenePro第5版程序。 10个apo 序列中，24/49个序列中有5个或5个以上的氨基酸相同或保守 岗位 最保守的区域是N-末端的位置1-26。 保守基序（Y，L/I/V/M，X，X，V/L/I）占据位置22-26。 在HSA中有15-16个保守的氨基酸残基与其同源， TTR和TBG仅为9-11（相差50%）。 A 25 a.一段HSA， 同源性>40%。 因此，我们已经证明， T4结合结构域之间的广泛同源性，即使在远亲中也是如此。 proteins. 甲状腺激素脂蛋白的潜在生理意义 在《趋势》中的一个特邀评论中讨论了这种相互作用， 内分泌和代谢。 我们以前的工作表明， 与LDL结合促进甲状腺素进入人成纤维细胞 并由apoB/apoE细胞表面受体介导。 实验 正在将这些观察结果扩展到人类肝细胞， 以确定脂蛋白是否参与甲状腺的排出， 从细胞中分泌激素。

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.