7vi5

Electron crystallographic structure of TIA-1 prion-like domain, wild type sequence

spinqualitylabelsall models 7vi5, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7vi5 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 1.761Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TIA1_HUMAN Involved in alternative pre-RNA splicing and regulation of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs). Possesses nucleolytic activity against cytotoxic lymphocyte target cells. May be involved in apoptosis. Publication Abstract from PubMed T cell intracellular antigen-1 (TIA-1) plays a central role in stress granule (SG) formation by self-assembly via the prion-like domain (PLD). In the TIA-1 PLD, amino acid mutations associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) or Welander distal myopathy (WDM), have been identified. However, how these mutations affect PLD self-assembly properties has remained elusive. In this study, we uncovered the implicit pathogenic structures caused by the mutations. NMR analysis indicated that the dynamic structures of the PLD are synergistically determined by the physicochemical properties of amino acids in units of five residues. Molecular dynamics simulations and three-dimensional electron crystallography, together with biochemical assays, revealed that the WDM mutation E384K attenuated the sticky properties, whereas the ALS mutations P362L and A381T enhanced the self-assembly by inducing beta-sheet interactions and highly condensed assembly, respectively. These results suggest that the P362L and A381T mutations increase the likelihood of irreversible amyloid fibrillization after phase-separated droplet formation, and this process may lead to pathogenicity. ALS mutations in the TIA-1 prion-like domain trigger highly condensed pathogenic structures.,Sekiyama N, Takaba K, Maki-Yonekura S, Akagi KI, Ohtani Y, Imamura K, Terakawa T, Yamashita K, Inaoka D, Yonekura K, Kodama TS, Tochio H Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2122523119. doi:, 10.1073/pnas.2122523119. Epub 2022 Sep 16. PMID:36112647 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA