Role of extracellular molecular chaperones in the folding of oxidized proteins - Refolding of colloidal thyroglobulin by protein disulfide isomerase and immunoglobulin heavy chain-binding protein
Role of extracellular molecular chaperones in the folding of oxidized proteins - Refolding of colloidal thyroglobulin by protein disulfide isomerase and immunoglobulin heavy chain-binding protein
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DOI：
10.1074/jbc.m101086200
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发表时间：
2001-06-15
影响因子：
4.8
通讯作者：
Lejeune, PJ
中科院分区：
文献类型：
--
作者：
Delom, F;Mallett, B;Lejeune, PJ
甲状腺激素的合成过程发生在甲状腺滤泡的内腔中，由氧化反应引起，作为副作用，导致甲状腺球蛋白（TG）（甲状腺激素原）的多聚化。虽然激素合成是一个连续的过程; Tg多聚体的量相对恒定。在此，我们研究了存在于卵泡腔中的两种分子伴侣，蛋白质二硫键异构酶（PDI）和免疫球蛋白重链结合蛋白（BiP），在使用天然Tg及其N端结构域（NTD）的氧化引起的多聚化过程中的作用。在体外，PDI减少Tg的多聚化，甚至抑制NTD多聚体的形成。在相同条件下，BiP能够与Tg和NTD多聚体结合，但不影响多聚化过程。将BiP与PDI结合并不增强PDL限制由氧化产生的多聚体形成的能力。然而，当BiP和PDI与多聚体形式一起反应并且反应更长时间（48 h）时，BiP大大增加了PDI的效率。这两种分子伴侣可能顺序地作用于分子间二硫键的还原。在甲状腺中，类似的过程也可能是有效的，并参与限制胶体中存在的Tg多聚体的量。这些结果表明，细胞外分子伴侣发挥类似的作用，发生在内质网，而且，参与控制的多聚化和聚集的蛋白质形成的氧化。
The process of thyroid hormone synthesis, which occurs in the lumen of the thyroid follicles, results from an oxidative reaction leading, as side effects, to the multimerization of thyroglobulin (TG), the prothyroid hormone, Although hormone synthesis is a continuous process; the amount of Tg multimers is relatively constant. Here, we investigated the role of two molecular chaperones, protein disulfide isomerase (PDI) and immunoglobulin heavy chain-binding protein (BiP), present in the follicular lumen, on the multimerization process due to oxidation using both native Tg and its N-terminal domain (NTD), In vitro, PDI decreased multimerization of Tg and even suppressed the formation of NTD multimers, Under the same conditions, BiP was able to bind to Tg and NTD multimers but did not affect the process of multimerization, Associating BiP with PDI did not enhance the ability of PDL to limit the formation of multimers produced by oxidation, However, when BiP and PDI were reacted together with the multimeric forms and for a longer time (48 h), BiP greatly increased the efficiency of PDI, Accordingly, these two molecular chaperones probably act sequentially on the reduction of the intermolecular disulfide bridges. In the thyroid, a similar process may also be effective and participate in limiting the amount of Tg multimers present in the colloid. These results suggest that extracellular molecular chaperones play a similar role to that occurring in the endoplasmic reticulum and, furthermore, take part in the control of multimerization and aggregation of proteins formed by oxidation.