Power D M, Elias N P, Richardson S J, Mendes J, Soares C M, Santos C R
Centro de Ciências de MAR (CCMAR), Universidade do Algarve, Campus de Gambelas, 8000 Faro, Portugal.
Gen Comp Endocrinol. 2000 Sep;119(3):241-55. doi: 10.1006/gcen.2000.7520.
Transthyretin (TTR) belongs to a group of proteins, which includes thyroxine-binding globulin and albumin, that bind to and transport thyroid hormones in the blood. TTR is also indirectly implicated in the carriage of vitamin A through the mediation of retinol-binding protein (RBP). It was first identified in 1942 in human serum and cerebrospinal fluid and was formerly called prealbumin for its ability to migrate faster than serum albumin on electrophoresis of whole plasma. It is a single polypeptide chain of 127 amino acids (14,000 Da) and is present in the plasma as a tetramer of noncovalently bound monomers. The major sites of synthesis of TTR in eutherian mammals, marsupials, and birds are the liver and choroid plexus but in reptiles it is synthesised only in the choroid plexus. The observation that TTR is strongly expressed in the choroid plexus but not in the liver of the stumpy-tailed lizard and the strong conservation of expression in the choroid plexus from reptiles to mammals have been taken as evidence to suggest that extrahepatic synthesis of TTR evolved first. The identification and cloning of TTR from the liver of an amphibian, Rana catesbeiana, and a teleost fish, Sparus aurata, and its absence from the choroid plexus of both species suggest an alternative model for its evolution. Protein modelling studies are presented that demonstrate differences in the electrostatic characteristics of the molecule in human, rat, chicken, and fish, which may explain why, in contrast to TTR from human and rat, TTR from fish and birds preferentially binds triiodo-l-thyronine.
转甲状腺素蛋白（TTR）属于一组蛋白质，其中包括甲状腺素结合球蛋白和白蛋白，它们在血液中结合并运输甲状腺激素。TTR还通过视黄醇结合蛋白（RBP）的介导间接参与维生素A的运输。它于1942年首次在人血清和脑脊液中被鉴定出来，由于其在全血浆电泳中迁移速度比血清白蛋白快，以前被称为前白蛋白。它是一条由127个氨基酸组成的单多肽链（14,000道尔顿），以非共价结合单体的四聚体形式存在于血浆中。在真兽类哺乳动物、有袋动物和鸟类中，TTR的主要合成部位是肝脏和脉络丛，但在爬行动物中，它仅在脉络丛中合成。短尾蜥蜴的脉络丛中TTR强烈表达而肝脏中不表达，以及从爬行动物到哺乳动物脉络丛中表达的高度保守性，这些观察结果被视为证据，表明TTR的肝外合成首先进化。从两栖动物牛蛙和硬骨鱼金头鲷的肝脏中鉴定和克隆出TTR，而这两个物种的脉络丛中均未发现TTR，这提示了其进化的另一种模式。本文展示了蛋白质建模研究，该研究证明了人类、大鼠、鸡和鱼类分子静电特性的差异，这可能解释了为什么与人类和大鼠的TTR不同，鱼类和鸟类的TTR优先结合三碘 - L - 甲状腺原氨酸。
