Importin α2 association with chromatin: Direct DNA binding via a novel DNA-binding domain
Importin α2 association with chromatin: Direct DNA binding via a novel DNA-binding domain
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DOI：
10.1111/gtc.12896
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发表时间：
2021-09-24
期刊：
影响因子：
2.1
通讯作者：
Yasuhara，Noriko
中科院分区：
文献类型：
--
作者：
Jibiki，Kazuya;Kodama，Takashi S.;Yasuhara，Noriko
蛋白质的核运输对于促进适当的核功能是重要的。Importinα家族蛋白作为大量核蛋白的转运受体，在核转运过程中起着关键作用。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，Importinα的这些非转运功能还没有被完全了解，特别是它们在分子水平上的机制和与染色质一起发挥作用的后果。在这里，我们报道了Importinα与染色质中不同的DNA序列结合的新的分子特征。我们新发现并鉴定了ImportinαN-末端的一个DNA结合域--核酸结合滑车极域(NAAT域)，该结构域位于传统的Importinβ结合域(IBB)中，是货物蛋白核运输所必需的。此外，我们还发现，Importinα的DNA结合协同偶联了其货物蛋白到DNA上的募集。这是首次通过NAAT结构域描述Importinα与染色质α之间的相互作用，表明Importin DNA N末端区域具有核转运和染色质结合的双功能。
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.