The nuclear transport of proteins is important for facilitating appropriate nuclear functions. The importin α family proteins play key roles in nuclear transport as transport receptors for copious nuclear proteins. Additionally, these proteins possess other functions, including chromatin association and gene regulation. However, these nontransport functions of importin α are not yet fully understood, especially their molecular-level mechanisms and consequences for functioning with chromatin. Here, we report the novel molecular characteristics of importin α binding to diverse DNA sequences in chromatin. We newly identified and characterized a DNA-binding domain—the Nucleic Acid Associating Trolley pole domain (NAAT domain)—in the N-terminal region of importin α within the conventional importin β binding (IBB) domain that is necessary for nuclear transport of cargo proteins. Furthermore, we found that the DNA binding of importin α synergistically coupled the recruitment of its cargo protein to DNA. This is the first study to delineate the interaction between importin α and chromatin DNA via the NAAT domain, indicating the bifunctionality of the importin α N-terminal region for nuclear transport and chromatin association.

中文翻译：

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Importin α2 与染色质的结合：通过新的 DNA 结合域直接结合 DNA

蛋白质的核转运对于促进适当的核功能很重要。importin α 家族蛋白作为大量核蛋白的转运受体在核转运中起关键作用。此外，这些蛋白质还具有其他功能，包括染色质结合和基因调控。然而，输入蛋白 α 的这些非转运功能尚未完全了解，尤其是它们的分子水平机制和染色质功能的后果。在这里，我们报告了 importin α 与染色质中不同 DNA 序列结合的新分子特征。我们新发现并表征了一个 DNA 结合域 - 核酸相关电车杆域 (NAAT 域) - 在常规输入蛋白 β 结合 (IBB) 域内输入蛋白 α 的 N 末端区域，这是核运输货物所必需的蛋白质。此外，我们发现 importin α 的 DNA 结合协同地将其货物蛋白募集到 DNA 上。这是第一项通过 NAAT 结构域描述 importin α 和染色质 DNA 之间相互作用的研究，表明 importin α N-末端区域对核转运和染色质结合的双功能。