Fig. 1. TDP-43 CTD self-associates and forms transient helical structures. (A) Domain structure of TDP-43. (B) α-Helical content of TDP-43 simulations at each residue, where single chain comes from a separate simulation of a single TDP-43 310-350 chain (single chain, black), and the other three curves from a two-chain

Six segments from TDP-43 LCD form steric zippers For structural studies, we targeted segments throughout the LCD because there is no consensus of which region is the amyloidogenic core. The LCD of

TDP-43 is an important pathological protein that aggregates in the diseased neuronal cells and is linked to various neurodegenerative disorders. In normal cells, TDP-43 is primarily an RNA-binding protein; however, how the dimeric TDP-43 binds RNA via its two RNA recognition motifs, RRM1 and RRM2, is not clear.

This double-spiral fold is formed by 79 amino-acid residues of TDP-43, extending from position 282 (a glycine) to position 360 (a glutamine). This region lies in a domain of TDP-43 that has been

The structure of a TDP-43 construct comprising both RRMs (amino acids 102–269) bound to UG-rich RNA oligonucleotide, AUG12 (5′-GUGUGAAUGAAU-3′), 

27/01/  · We show that TDP-43 is a dimeric protein with two RRM domains, both involved in DNA and RNA binding. The crystal structure reveals the basis of TDP-43's TG/UG preference in nucleic acids binding. It also reveals that RRM2 domain has an atypical RRM-fold with an additional β-strand involved in making protein–protein interactions.

TAR DNA-binding protein of 43 kDa (TDP-43) is an essential RNA-binding protein, self-assembles into prion-like aggregates, and is known to be the structural 

23/10/  · Aggregates of the TAR DNA binding protein 43 (TDP-43), are hallmark features of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD), with overlapping clinical, genetic and pathological features. TDP-43 and Neurodegeneration: From Bench to Bedside

Solution structure of TDP-43 N-terminal domain dimer. 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.

TDP-43 belongs to the family of heterogeneous nuclear ribonucleoproteins (hnRNPs) that play important roles in RNA regulation. While the complete 3D structure 

Cryo-EM Structure of TDP-43 polymorphic fibrils. a, Schematic of full-length TDP-43. SegA (residues 311-360) and SegB (residues 286-331) identified for structural determination are shown as gray bars, respectively above and below the low-complexity domain (LCD). The color bars show the range of residues visualized in the structure of each