Inherently disordered regions of axonemal dynein assembly factors.
Inherently disordered regions of axonemal dynein assembly factors.
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DOI：
10.1002/cm.21789
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发表时间：
2023-09
期刊：
影响因子：
2.9
通讯作者：
Stephen M King
中科院分区：
文献类型：
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作者：
Stephen M King
动力蛋白驱动的纤毛跳动需要移动单个细胞，并在表面和空洞内产生流体流动。这些马达酶高度复杂，可以包含20多种不同的蛋白质成分，总质量接近2丙二醛。动力蛋白重链是由~4500个残基组成的巨大蛋白质，核糖体大约需要15分钟才能合成一个。从绿藻、衣藻到人类等一系列生物的研究已经确定了19种胞浆因子(DNAAFs)，它们是专门构建轴丝动力蛋白所必需的；其中许多蛋白质的缺陷会导致哺乳动物的原发纤毛运动障碍，从而导致不孕不育、严重的支气管问题和内翻。这些因素如何在时间和空间上相互调控地促进动力蛋白在细胞质中的组装仍然是一个非常不确定的问题。这些DNAAFs包含各种折叠良好的结构域，其中许多结构域提供了蛋白质相互作用的表面。然而，许多也显示出被预测为天生无序的大区域。在这里，我将讨论这些非结构化片段的性质，它们驱动蛋白质相分离的预测倾向，以及它们在动力蛋白组装过程中采用更明确构象的可能性。
The dynein-driven beating of cilia is required to move individual cells and to generate fluid flow across surfaces and within cavities. These motor enzymes are highly complex and can contain upwards of 20 different protein components with a total mass approaching 2 MDa. The dynein heavy chains are enormous proteins consisting of ~4500 residues and ribosomes take approximately 15 min to synthesize one. Studies in a broad array of organisms ranging from the green alga Chlamydomonas to humans has identified 19 cytosolic factors (DNAAFs) that are needed to specifically build axonemal dyneins; defects in many of these proteins lead to primary ciliary dyskinesia in mammals which can result in infertility, severe bronchial problems, and situs inversus. How all these factors cooperate in a spatially and temporally regulated manner to promote dynein assembly in cytoplasm remains very uncertain. These DNAAFs contain a variety of well-folded domains many of which provide protein interaction surfaces. However, many also exhibit large regions that are predicted to be inherently disordered. Here I discuss the nature of these unstructured segments, their predicted propensity for driving protein phase separation, and their potential for adopting more defined conformations during the dynein assembly process.