The TDP-43 N-terminal domain structure at high resolution
نویسندگان
چکیده
منابع مشابه
Electrostatic Repulsion Governs TDP-43 C-terminal Domain Aggregation
TDP-43 is a protein with multiple crucial functions in RNA processing and mRNA-protein (mRNP) particle formation, two processes that are strongly implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD) [1]. The recently published structural characterization by Lim, Wei, Lu, and Song [2] of the complete (residues 262–414) C-terminal domain (CTD) of TDP-43 and t...
متن کاملExpression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies.
The disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) was identified recently as the TDP-43 (TAR DNA-binding protein 43), thereby providing a molecular link between these two disorders. In FTLD-U and ALS, TDP-43 is redistributed from its normal nuclear localization to form cytoplasmic insoluble aggregates. Mo...
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Yersinia pestis, the causative agent of bubonic plague, injects effector proteins into the cytosol of mammalian cells that enable the bacterium to evade the immune response of the infected organism by interfering with eukaryotic signal transduction pathways. YopH is a modular effector composed of a C-terminal protein tyrosine phosphatase (PTPase) domain and a multifunctional N-terminal domain t...
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RNA-binding protein TDP-43 mediates essential RNA processing but forms cytoplasmic neuronal inclusions via its C-terminal domain (CTD) in amyotrophic lateral sclerosis (ALS). It remains unclear if aggregated TDP-43 is neurotoxic and if ∼50 ALS-associated missense mutations in TDP-43 CTD promote aggregation, or if loss of normal function plays a role in disease. Recent work points to the ability...
متن کاملA single N‐terminal phosphomimic disrupts TDP‐43 polymerization, phase separation, and RNA splicing
TDP-43 is an RNA-binding protein active in splicing that concentrates into membraneless ribonucleoprotein granules and forms aggregates in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Although best known for its predominantly disordered C-terminal domain which mediates ALS inclusions, TDP-43 has a globular N-terminal domain (NTD). Here, we show that TDP-43 NTD assembles into hea...
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ژورنال
عنوان ژورنال: The FEBS Journal
سال: 2016
ISSN: 1742-464X
DOI: 10.1111/febs.13651