BackgroundThe motor protein dynein is integral to retrograde transport along microtubules and interacts with numerous cargoes through the recruitment of cargo‐specific adaptor proteins. This interaction is mediated by dynein light intermediate chain subunits LIC1 (DYNC1LI1) and LIC2 (DYNC1LI2), which govern the adaptor binding and are present in distinct dynein complexes with overlapping and unique functions.MethodsUsing bioinformatics, we analyzed the C‐terminal domains (CTDs) of LIC1 and LIC2, revealing similar structural features but diverse post‐translational modifications (PTMs). The methylation status of LIC2 and the proteins involved in this modification were examined through immunoprecipitation and immunoblotting analyses. The specific methylation sites on LIC2 were identified through a site‐directed mutagenesis analysis, contributing to a deeper understanding of the regulatory mechanisms of the dynein complex.ResultsWe found that LIC2 is specifically methylated at the arginine 397 residue, a reaction that is catalyzed by protein arginine methyltransferase 1 (PRMT1).ConclusionsThe distinct PTMs of the LIC subunits offer a versatile mechanism for dynein to transport diverse cargoes efficiently. Understanding how these PTMs influence the functions of LIC2, and how they differ from LIC1, is crucial for elucidating the role of dynein‐related transport pathways in a range of diseases. The discovery of the arginine 397 methylation site on LIC2 enhances our insight into the regulatory PTMs of dynein functions.

中文翻译：

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动力蛋白轻中间链表现出不同的精氨酸甲基化模式

背景运动蛋白动力蛋白是沿微管逆行运输的组成部分，并通过招募货物特异性接头蛋白与众多货物相互作用。这种相互作用是由动力蛋白轻中间链亚基 LIC1 (DYNC1LI1) 和 LIC2 (DYNC1LI2) 介导的，它们控制接头结合，并存在于具有重叠和独特功能的不同动力蛋白复合物中。方法使用生物信息学，我们分析了 C 末端结构域 (CTD) ）的 LIC1 和 LIC2，揭示了相似的结构特征，但翻译后修饰（PTM）不同。通过免疫沉淀和免疫印迹分析检查了 LIC2 的甲基化状态和参与这种修饰的蛋白质。通过定点突变分析鉴定了LIC2上的特定甲基化位点，有助于更深入地了解动力蛋白复合物的调控机制。结果我们发现LIC2在精氨酸397残基处被特异性甲基化，这是由蛋白质催化的反应精氨酸甲基转移酶 1 (PRMT1)。结论 LIC 亚基的独特 PTM 为动力蛋白有效运输不同的货物提供了一种多功能机制。了解这些 PTM 如何影响 LIC2 的功能，以及它们与 LIC1 有何不同，对于阐明动力蛋白相关转运途径在一系列疾病中的作用至关重要。 LIC2 上精氨酸 397 甲基化位点的发现增强了我们对动力蛋白功能调节 PTM 的了解。