Supply of iron into human cells is achieved by iron carrier protein transferrin and its receptor that upon complex formation get internalized by endocytosis. Similarly, the iron needs to be delivered into the brain, and necessitates the transport across the blood‐brain barrier. While there are still unanswered questions about these mechanisms, extensive efforts have been made to use the system for delivery of therapeutics into biological compartments. The dimeric form of the receptor, where each subunit consists of three domains, further complicates the detailed investigation of molecular determinants responsible for guiding the receptor interactions with other proteins. Especially the apical domain's biological function has been elusive. To further the study of transferrin receptor, we have computationally decoupled the apical domain for soluble expression, and validated the design strategy by structure determination. Besides presenting a methodology for solubilizing domains, the results will allow for study of apical domain's function.

中文翻译：

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计算主干设计实现了转铁蛋白受体顶端结构域的可溶性工程。


人体细胞中的铁供应是通过铁载体蛋白转铁蛋白及其受体实现的，复合物形成后通过内吞作用内化。同样，铁需要输送到大脑中，并且需要穿过血脑屏障。虽然关于这些机制仍然存在未解答的问题，但人们已经做出了广泛的努力来使用该系统将治疗剂输送到生物区室中。受体的二聚体形式，其中每个亚基由三个结构域组成，使负责引导受体与其他蛋白质相互作用的分子决定因素的详细研究变得更加复杂。尤其是顶端域的生物学功能一直难以捉摸。为了进一步研究转铁蛋白受体，我们通过计算解耦了可溶性表达的顶端结构域，并通过结构测定验证了设计策略。除了提出溶解域的方法之外，结果还将允许研究顶端域的功能。