CCDC103 is a small protein with unusual biophysical properties that is required for outer dynein arm assembly on ciliary axonemes. Mutations in both human and zebrafish CCDC103 proteins lead to primary ciliary dyskinesia. Previous studies revealed that this protein can oligomerize and appears to be arrayed along the entire length of the ciliary axoneme. CCDC103 also binds purified microtubules directly and indeed stabilizes them. Here we use biochemical approaches to identify two regions of CCDC103 that mediate self‐interaction. In both cases, these associations are stable to heating in the presence of detergent and are not disrupted by strong reducing agents. One interaction region consists of a 27‐residue inherently disorder segment that can mediate heat/detergent‐resistant dimerization when attached to unrelated monomeric proteins. The second interface includes the C‐terminal RPAP3_C alpha helical domain. Our data suggest that CCDC103 can form an unconventional polymer and we propose models for how the monomers might be organized. We also use molecular modeling of the RPAP3_C domain to determine the structural consequences of the pathogenic H154P mutation found in human PCD patients.

中文翻译：

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外部动力蛋白臂装配因子CCDC103通过多个自相互作用位点形成分子支架。

CCDC103是一种具有异常生物物理特性的小蛋白，是睫状轴突上外部动力蛋白臂装配所必需的。人和斑马鱼CCDC103蛋白中的突变都会导致原发性睫状运动障碍。先前的研究表明，这种蛋白质可以寡聚，并且似乎沿着睫状轴突的整个长度排列。CCDC103还直接结合纯化的微管，并确实稳定它们。在这里，我们使用生化方法来识别CCDC103介导自我相互作用的两个区域。在两种情况下，这些缔合在洗涤剂存在下对加热都是稳定的，并且不会被强还原剂破坏。一个相互作用区域由一个27个残基的固有无序片段组成，当与无关的单体蛋白连接时，该片段可以介导耐热/耐洗涤剂的二聚作用。第二个接口包括C端RPAP3_C alpha螺旋结构域。我们的数据表明CCDC103可以形成非常规聚合物，我们提出了单体如何组织的模型。我们还使用RPAP3_C域的分子建模来确定在人PCD患者中发现的病原性H154P突变的结构后果。