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NMR assignments for the C-terminal domain of human TDP-43
Biomolecular NMR Assignments ( IF 0.8 ) Pub Date : 2021-01-08 , DOI: 10.1007/s12104-020-10002-7
David Pantoja-Uceda 1 , Cristiana Stuani 2 , Douglas V Laurents 1 , Ann E McDermott 3 , Emanuele Buratti 2 , Miguel Mompeán 1, 3
Affiliation  

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a 414-residue protein whose aberrant aggregation is implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). Intriguingly, TDP-43 has also been shown to functionally oligomerize to carry out physiological functions. TDP-43 also exists in mixed condensates or granules with other proteins (e.g. neuronal or stress granules), and its large C-terminal domain (CTD, residues 267–414) seems responsible for TDP-43 both homo- and heterotypic interactions underlying such diverse functional and pathological aggregation events. A myriad of distinct triggers may drive TDP-43 oligomerization, including interaction partners or changes in pH or salinity. In this Assignment Note, we report the complete backbone and a wealth of side chain chemical shift assignments for the CTD of TDP-43 at pH 4. The assignments presented here provide a solid starting point to study the aggregation pathway of TDP-43 at pH values below those considered physiological but relevant in pathological settings, and to contrast the aggregation behaviour under distinct conditions and in the presence of interacting partners.



中文翻译:


人 TDP-43 C 末端结构域的 NMR 归属



43 kDa 的交互反应 DNA 结合蛋白 (TDP-43) 是一种 414 个残基的蛋白质,其异常聚集与神经退行性疾病有关,包括肌萎缩侧索硬化症 (ALS) 或额颞叶变性 (FTLD)。有趣的是,TDP-43 还被证明可以通过功能性寡聚来发挥生理功能。 TDP-43 还存在于与其他蛋白质(例如神经元或应激颗粒)的混合凝聚物或颗粒中,其大的 C 末端结构域(CTD,残基 267-414)似乎与 TDP-43 的同型和异型相互作用有关。多种功能性和病理性聚集事件。无数不同的触发因素可能驱动 TDP-43 寡聚化,包括相互作用伙伴或 pH 或盐度的变化。在本作业笔记中,我们报告了 TDP-43 在 pH 4 下的 CTD 的完整主链和大量侧链化学位移作业。此处介绍的作业为研究 TDP-43 在 pH 下的聚集途径提供了坚实的起点低于那些被认为是生理但与病理环境相关的值,并对比不同条件下和存在相互作用伙伴的情况下的聚集行为。

更新日期:2021-01-08
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