6cf4

Segment NFGTFS, with familial mutation A315T and phosphorylated threonine, from the low complexity domain of TDP-43, residues 312-317Segment NFGTFS, with familial mutation A315T and phosphorylated threonine, from the low complexity domain of TDP-43, residues 312-317

Structural highlights 6cf4 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron crystallography, Resolution 0.75Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TADBP_HUMAN Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:612069. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Function TADBP_HUMAN DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR. Publication Abstract from PubMed The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of beta-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible beta-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation. Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.,Guenther EL, Cao Q, Trinh H, Lu J, Sawaya MR, Cascio D, Boyer DR, Rodriguez JA, Hughes MP, Eisenberg DS Nat Struct Mol Biol. 2018 May 21. pii: 10.1038/s41594-018-0064-2. doi:, 10.1038/s41594-018-0064-2. PMID:29786080 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6cf4, resolution 0.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image