Disulfide-linked aggregation of thyroglobulin normally occurs during nascent protein folding.
Disulfide-linked aggregation of thyroglobulin normally occurs during nascent protein folding.
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甲状腺球蛋白的二硫键连接聚集通常发生在新生蛋白质折叠过程中。
DOI：
10.1152/ajpcell.1993.265.3.c704
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Arvan,P
中科院分区：
文献类型：
--
作者：
Kim,PS;Kim,KR;Arvan,P
在培养的猪甲状腺细胞的内质网（ER）中，新合成的甲状腺球蛋白（Tg，甲状腺激素合成的前体）最初形成蛋白质聚集体，溶解成单体，然后组装成二聚体，然后在细胞内运输和分泌。然而，研究表明，在不同的生理状态和不同的细胞中，内质网的折叠效率可能会有所不同；考虑到这一点，我们开始进一步描述新生 Tg 聚集现象的特征。在原代培养的甲状腺细胞、新鲜甲状腺滤泡组织（猪和大鼠来源）和 FRTL-5 细胞系中，新生 Tg 似乎与错误配对的链间二硫键短暂聚集。使用最大限度抑制蛋白水解以及人为二硫键形成的细胞裂解程序，可以通过凝胶过滤稳定分离 M(r) > 或 = 2,000,000 的 Tg 聚集体。此外，促甲状腺素和其他增强 Tg 产生的激素的刺激可能会改变但不会消除这些聚集体的形成。我们得出的结论是，短暂的二硫键连接聚集通常发生在甲状腺上皮细胞 ER 的 Tg 折叠过程中。
In the endoplasmic reticulum (ER) of cultured porcine thyrocytes, newly synthesized thyroglobulin (Tg, the precursor in thyroid hormone synthesis) initially forms protein aggregates, which are dissolved into monomers and then assembled to dimers, before intracellular transport and secretion. However, studies suggest that in different physiological states and in different cells, folding efficiency in the ER may vary; with this in mind we have set out to further characterize the phenomenon of nascent Tg aggregation. In primary cultured thyrocytes, fresh thyroid follicular tissue (of porcine and rat origin), and the FRTL-5 cell line, nascent Tg appears transiently aggregated with mispaired, interchain disulfide linkages. Using a cell lysis procedure that maximally inhibits proteolysis as well as artifactual disulfide formation, Tg aggregates of M(r) > or = 2,000,000 can be stably isolated by gel filtration. Furthermore, stimulation with thyrotropin and other hormones that enhance Tg production may alter but does not eliminate formation of these aggregates. We conclude that transient disulfide-linked aggregation occurs normally during Tg folding in the ER of thyroid epithelial cells.