Institute for Molecular Biosciences and Biomolecular Resonance Center (BMRZ) of Goethe University Frankfurt, Max-von-Laue-Str. 7-9, 60438, Frankfurt am Main, Germany.
IMPRS on Cellular Biophysics, Max-von-Laue-Str. 7-9, 60438, Frankfurt am Main, Germany.
Biomol NMR Assign. 2023 Jun;17(1):121-127. doi: 10.1007/s12104-023-10130-w. Epub 2023 May 2.
The family of AT-rich interactive domain (ARID) containing proteins -Arids- contains 15 members that have almost exclusively been described as DNA-binding proteins. Interestingly, a decade ago the family member Arid5a was found to bind and stabilize mRNAs of immune system key players and thereby account for driving inflammatory and autoimmune diseases. How exactly binding to DNA and RNA is coordinated by the Arid5a ARID domain remains unknown, mainly due to the lack of atom-resolved information on nucleic acid-binding. This in particular applies to the protein's ARID domain, despite the comfortable size of its core unit for NMR-based investigations. Furthermore, the core domain of ARID domains is found to be extended by functionally relevant, often flexible stretches, but whether such elongations are present and crucial for the versatile Arid5a functions is unknown. We here provide a near-complete NMR backbone resonance assignment of the Arid5a ARID domain with N- and C-terminal extensions, which serves as a basis for further studies of its nucleic acid-binding preferences and targeted inhibition by means of NMR. Our data thus significantly contribute to unravelling mechanisms of Arid5a-mediated gene regulation and diseases.
富含 AT 的相互作用结构域（ARID）家族的蛋白 -Arids- 包含 15 个成员，它们几乎都是 DNA 结合蛋白。有趣的是，十年前发现 ARID 家族成员 Arid5a 可以结合和稳定免疫系统关键因子的 mRNA，从而导致炎症和自身免疫性疾病。Arid5a 的 ARID 结构域如何与 DNA 和 RNA 的结合进行协调尚不清楚，主要是因为缺乏关于核酸结合的原子分辨率信息。这在很大程度上适用于该蛋白的 ARID 结构域，尽管其核心单元非常适合进行基于 NMR 的研究。此外，ARID 结构域的核心结构域被发现通过功能相关的、通常是灵活的延伸而扩展，但这种延伸是否存在且对多功能 Arid5a 功能至关重要尚不清楚。我们在此提供了带有 N 端和 C 端延伸的 Arid5a ARID 结构域的近完整 NMR 骨架共振分配，这为进一步研究其核酸结合偏好以及通过 NMR 进行靶向抑制提供了基础。我们的数据因此为揭示 Arid5a 介导的基因调控和疾病的机制做出了重要贡献。
