1 H, 13 C and 15 N resonance assignments and solution structures of the two RRM domains of Matrin-3
1 H, 13 C and 15 N resonance assignments and solution structures of the two RRM domains of Matrin-3
复制标题
Matrin-3 两个 RRM 结构域的 1 H、 13 C 和 15 N 共振分配和溶液结构
DOI：
10.1007/s12104-021-10057-0
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Muto Y.
中科院分区：
文献类型：
--
作者：
He F;Kuwasako K;Takizawa M;Takahashi M;Tsuda K;Nagata T;Watanabe S;Tanaka A;Kobayashi N;Kigawa T;Guntert P;Shirouzu M;Yokoyama S;Muto Y.
Matrin-3是一种多功能蛋白质，可以与DNA和RNA结合。它的DNA结合活性与核基质的形成和转录调控有关，而它的RNA结合活性与mRNA代谢有关，包括剪接、运输、稳定和降解。相应地，Matrin-3有两个用于DNA结合的锌指结构域和两个连续的RNA识别基序(RRM)结构域用于RNA结合。Matrin-3被报道会导致肌萎缩侧索硬化症(ALS)和额颞部痴呆(FTD)，因为它的无序区域含有致病突变。同时，研究表明，Matrin-3的RRM结构域介导的RNA结合活性影响不溶性细胞质颗粒的形成，这与ALS/FTD的致病机制有关。因此，为了全面了解ALS/FTD，必须澄清RRM结构域对浓缩蛋白质/RNA混合物相分离的影响。在这里，我们报告了两个RNA结合域的1H，15N和13C共振指定及其溶液结构。本工作获得的共振归属和溶液结构将有助于阐明Matrin-3在ALS和/或FTD发病机制中的分子基础。
Matrin-3 is a multifunctional protein that binds to both DNA and RNA. Its DNA-binding activity is linked to the formation of the nuclear matrix and transcriptional regulation, while its RNA-binding activity is linked to mRNA metabolism including splicing, transport, stabilization, and degradation. Correspondingly, Matrin-3 has two zinc finger domains for DNA binding and two consecutive RNA recognition motif (RRM) domains for RNA binding. Matrin-3 has been reported to cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) when its disordered region contains pathogenic mutations. Simultaneously, it has been shown that the RNA-binding activity of Matrin-3 mediated by its RRM domains, affects the formation of insoluble cytoplasmic granules, which are related to the pathogenic mechanism of ALS/FTD. Thus, the effect of the RRM domains on the phase separation of condensed protein/RNA mixtures has to be clarified for a comprehensive understanding of ALS/FTD. Here, we report the1H,15N, and13C resonance assignments of the two RNA binding domains and their solution structures. The resonance assignments and the solution structures obtained in this work will contribute to the elucidation of the molecular basis of Matrin-3 in the pathogenic mechanism of ALS and/or FTD.