Yamauchi K, Takeuchi H, Overall M, Dziadek M, Munro S L, Schreiber G
Department of Biology, Faculty of Science, Shizuoka University, Japan.
Eur J Biochem. 1998 Sep 1;256(2):287-96. doi: 10.1046/j.1432-1327.1998.2560287.x.
Transthyretin, an extracellular thyroid-hormone-binding protein (THBP) in higher vertebrates, is synthesized and secreted by the choroid plexus of all classes of vertebrates, except fish and amphibians, and synthesized in the liver of endothermic animals. Here, we report the nucleotide sequence of the cDNA for a THBP found in plasma of bullfrog (Rana catesbeiana) tadpoles before the climax of metamorphosis. The amino acid sequence clearly shows this protein to be an amphibian transthyretin. The three-dimensional structure of bullfrog transthyretin was derived using homology modeling. Compared with transthyretins from other vertebrate species, bullfrog transthyretin is highly conserved at the thyroid hormone-binding sites and other important structural regions of the subunits. Bullfrog transthyretin mRNA was found in tadpole liver, but not in tadpole choroid plexus. Thus, during evolution, synthesis of transthyretin in the liver of metamorphosing amphibians preceded that in the choroid plexus of reptiles, birds and mammals. It was previously observed that the protein most abundantly synthesized and secreted by the choroid plexus in adult amphibians is a lipocalin [Achen, M. G., Harms, P. J., Thomas, T., Richardson, S. J., Wettenhall, R. E. H. & Schreiber, G. (1992) J. Biol. Chem. 267, 23170-23174], in contrast to transthyretin being the most abundantly synthesized and secreted protein in the choroid plexus of mammals, birds and reptiles. Lipocalin mRNA was found in large amounts in tadpole choroid plexus, but not livers.
转甲状腺素蛋白是高等脊椎动物中的一种细胞外甲状腺激素结合蛋白（THBP），除鱼类和两栖动物外，所有脊椎动物的脉络丛都能合成并分泌该蛋白，而恒温动物的肝脏也能合成。在此，我们报告了在牛蛙（Rana catesbeiana）蝌蚪变态高峰期之前血浆中发现的一种THBP的cDNA核苷酸序列。氨基酸序列清楚地表明该蛋白是一种两栖类转甲状腺素蛋白。利用同源建模推导了牛蛙转甲状腺素蛋白的三维结构。与其他脊椎动物物种的转甲状腺素蛋白相比，牛蛙转甲状腺素蛋白在亚基的甲状腺激素结合位点和其他重要结构区域高度保守。在蝌蚪肝脏中发现了牛蛙转甲状腺素蛋白mRNA，但在蝌蚪脉络丛中未发现。因此，在进化过程中，变态期两栖动物肝脏中转甲状腺素蛋白的合成先于爬行动物、鸟类和哺乳动物脉络丛中的合成。此前观察到，成年两栖动物脉络丛中合成和分泌最多的蛋白质是一种脂质运载蛋白[Achen, M. G., Harms, P. J., Thomas, T., Richardson, S. J., Wettenhall, R. E. H. & Schreiber, G. (1992) J. Biol. Chem. 267, 23170 - 23174]，这与哺乳动物、鸟类和爬行动物脉络丛中合成和分泌最多的蛋白质是转甲状腺素蛋白形成对比。在蝌蚪脉络丛中发现大量脂质运载蛋白mRNA，但在肝脏中未发现。
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