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Importin α2 association with chromatin: Direct DNA binding via a novel DNA binding domain
bioRxiv - Molecular Biology Pub Date : 2020-11-24 , DOI: 10.1101/2020.05.04.075580
Kazuya Jibiki , Takashi S. Kodama , Atsushi Suenaga , Yota Kawase , Noriko Shibazaki , Shin Nomoto , Seiya Nagasawa , Misaki Nagashima , Shieri Shimodan , Renan Kikuchi , Noriko Saitoh , Yoshihiro Yoneda , Ken-ich Akagi , Noriko Yasuhara

Nuclear transport of proteins is important for facilitating appropriate nuclear functions. The proteins of the importin α family play key roles in nuclear transport as transport receptors for a huge number of nuclear proteins. Additionally, these proteins possess other functions, including chromatin association and gene regulation. However, these non-transport functions of importin α are not yet fully understood, especially their molecular-level mechanisms for functioning with chromatin and their consequences. Here, we report the novel molecular characteristics of importin α involving binding to diverse 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, which was shown to be necessary for nuclear transport of cargo proteins. We propose a 'stroll around and locate' model to explain the association of importin α with chromatin. 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:

Importinα2与染色质的缔合: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。importinα家族的蛋白质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,包括染色质缔合和基因调控。然而,尚未全面了解importinα的这些非转运功能,尤其是它们与染色质一起起作用的分子水平机制及其后果。在这里,我们报告了importinα的新分子特征,涉及与染色质中不同序列的结合。我们新近鉴定并表征了一个DNA结合域-常规importinβ结合(IBB)域内importinαN端区域的核酸缔合小车极域(NAAT域),它被证明对货物蛋白的核转运是必需的。我们提出了一种“漫步并定位”模型来解释importinα与染色质的关联。这是第一个通过NAAT域描述输入蛋白α和染色质DNA之间相互作用的研究,表明输入蛋白αN末端区域对核转运和染色质缔合具有双重功能。
更新日期:2020-11-25
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