Jibiki Kazuya, Kodama Takashi S, Suenaga Atsushi, Kawase Yota, Shibazaki Noriko, Nomoto Shin, Nagasawa Seiya, Nagashima Misaki, Shimodan Shieri, Kikuchi Renan, Okayasu Mina, Takashita Ruka, Mehmood Rashid, Saitoh Noriko, Yoneda Yoshihiro, Akagi Ken-Ichi, Yasuhara Noriko
Graduate School of Integrated Basic Sciences, Nihon University, Tokyo, Japan.
National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
Genes Cells. 2021 Dec;26(12):945-966. doi: 10.1111/gtc.12896. Epub 2021 Sep 24.
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.
蛋白质的核运输对于促进适当的核功能很重要。输入蛋白α家族蛋白作为大量核蛋白的运输受体，在核运输中起关键作用。此外，这些蛋白还具有其他功能，包括与染色质结合和基因调控。然而，输入蛋白α的这些非运输功能尚未完全了解，尤其是它们在分子水平上的机制以及与染色质相互作用的后果。在此，我们报道了输入蛋白α与染色质中不同DNA序列结合的新分子特征。我们在输入蛋白α的N端区域新鉴定并表征了一个DNA结合结构域——核酸结合手推车结构域（NAAT结构域），它位于传统的输入蛋白β结合（IBB）结构域内，是货物蛋白核运输所必需的。此外，我们发现输入蛋白α与DNA的结合协同促进了其货物蛋白向DNA的募集。这是第一项通过NAAT结构域描述输入蛋白α与染色质DNA之间相互作用的研究，表明输入蛋白α N端区域在核运输和染色质结合方面具有双功能性。
