[Thyroglobulin and the biosynthesis of thyroid hormones].
[Thyroglobulin and the biosynthesis of thyroid hormones].
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[甲状腺球蛋白和甲状腺激素的生物合成]。
DOI：
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发表时间：
1985
影响因子：
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通讯作者：
S. Lissitzky
中科院分区：
文献类型：
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作者：
S. Lissitzky
甲状腺球蛋白（分子量 660 kDa）是甲状腺的特定蛋白质，其中合成并储存甲状腺激素（甲状腺素和 3,5,3'-三碘甲状腺原氨酸）。它由大小相等的亚基 (330 kDa) 组成，每个亚基包含相同的多肽链，与代表蛋白质重量 8% 至 10% 的两种类型的寡糖单位相关联。本文报道的研究描述了甲状腺球蛋白中离散激素生成位点的存在。对蛋白质进行化学（CNBr）和酶（胰蛋白酶和金黄色葡萄球菌蛋白酶 V8）处理后，四种不同的含激素肽段被分离、纯化和测序。它们对应于蛋白质的含激素酪氨酸位点。一个酪氨酸位于该链的N端天冬酰胺的4个氨基酸残基处，是甲状腺素合成的主要位点。代表三碘甲状腺原氨酸位点的另一个位点位于 C 端赖氨酸之前的 2 个氨基酸处。最后，另外两个位点，一个对碘和甲状腺素形成具有低亲和力，另一个对碘和甲状腺素形成具有高亲和力，同样位于链的 C 末端部分。位于甲状腺球蛋白链相对远端的激素形成区域可能代表更容易碘化的区域，并且具有适合将碘酪氨酸偶联成碘甲状腺氨酸残基并最终被蛋白酶攻击以将游离激素释放到循环中的构象。不同碘亲和力的激素生成位点的存在使得甲状腺球蛋白能够根据外部碘供应适应性地调节其激素生成能力。这一过程的分子机制仍不清楚。
Thyroglobulin (mol. wt. 660 kDa) is the specific protein of the thyroid gland in which are synthesized and stored the thyroid hormones (thyroxine and 3,5,3'-triiodothyronine). It is formed of equal-sized subunits (330 kDa) containing each identical polypeptide chains to which are associated two types of oligosaccharide units representing 8 to 10% by weight of the protein. The studies reported in this paper describe the presence in thyroglobulin of discrete hormonogenic sites. After chemical (CNBr) and enzymatic (trypsin and protease V8 of S. aureus) treatments of the protein, four different hormone-containing peptide segments have been isolated, purified and sequenced. They correspond to the hormonogenic tyrosine-containing sites of the protein. One tyrosine is located at 4 amino acid residues from the N-terminal asparagine of the chain and is a major site for thyroxine synthesis. Another one which represents the triiodothyronine site is situated 2 amino acids before the C-terminal lysine. Finally, two other sites, one of low affinity and the other of high affinity for iodine and thyroxine formation, are equally located in the C-terminal part of the chain. The hormone-forming regions localized at the opposite far ends of the thyroglobulin chain(s) likely represent zones more accessible to iodination and with a conformation suited for the coupling of iodotyrosine into iodothyronine residues and ultimately protease attack to release the free hormones into the circulation. The presence of hormonogenic sites of different affinities for iodine allows thyroglobulin to modulate adaptively its hormonogenic capacity to external iodine supply. The molecular mechanism of this process is still unknown.