4. Arai, T. et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.Biochem. Biophys. Res. Commun.351, 602–611 (2006). 5. Arseni, D. et al. S...
Diana Arseni, et al.Structure of pathological TDP-43 filaments from ALS with FTLD. Article. 2021. Ariel Ionescu1, Topaz Altman1 and Eran Perlson. Looking for answers far away from the soma—the (un)known axonal functions of TDP-43, and their contribution to early NMJ disruption in ALS. M...
在最新发表于《Structure》期刊的研究中,布朗大学(Brown University)研究人员揭示了ALS突变如何在原子层面上破坏TDP-43蛋白质,导致其无法执行适当功能并形成聚合物。 “我们知道TDP-43的一部分会形成聚合物,而且在那个结构域存在50个突变。但是我们不知道那个结构域的功能,它是如何出错以及为什么会聚集”该研究通讯作者、...
TDP-43 is a conserved RNA binding protein with known roles in mRNA splicing and stability. Cytoplasmic deposition of TDP-43 has been linked to multiple neurodegenerative diseases, including ALS and frontotemporal lobar dementia (FTLD). We have engineered pan-neuronal expression of human TDP-43 ...
8 Conicella, A. E., Zerze, G. H., Mittal, J. & Fawzi, N. L. ALS Mutations Disrupt Phase Separation Mediated by alpha-Helical Structure in the TDP-43 Low-Complexity C-Terminal Domain.Structure24, 1537-1549...
An identical amyloid-like filament structure comprising a single protofilament was found in both brain regions and individuals. The ordered filament core spans residues 282–360 in the TDP-43 low-complexity domain and adopts a previously undescribed double-spiral-shaped fold, which shows no ...
Fig. 1. TDP-43 structure and the mutation regions causing ALS.TDP-43, a 414 amino acid length protein, consists of an N-terminal domain (NTD), two RNA recognition motifs (RRM1 and RRM2), and a C-terminal glycine-rich region. Identified mutations in TDP-43 identified from sporadic and ...
Fig. 1 Structure of TDP-43 protein. Numbers represent amino acid lengths of TDP-43. NLS: nuclear localization signal, RRM: RNA recognition motifs, NES: nuclear export signal, Q/N: glutamine/asparagine-rich domain, M1–M5: five putative mitochondrial localization signals ...
TDP-43 contains four structural regions, which are an N-terminal domain, two RNA recognition motifs (RRM1 and RRM2), and a C-terminal glycine-rich region (Fig.2a). TDP-43 may function as a homodimer via the interaction of N-terminal regions20,30, but the misfolded structure of TDP-43 ...
By performing systematic energy calculations, we reveal a prevailing trend of destabilizing effects induced by these mutations in the amyloid structure, challenging the traditionally assumed correlation between pathogenicity and amyloidogenic propensity. Understanding the molecular basis of this discrepancy ...