The SGYS motif of TAF15 prion-like domain is critical to amyloid fibril formation.

ABSTRACT: Misfolding of TATA-box binding protein-associated factor 15 (TAF15) may cause neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Some mutations of prion-like domain (PrLD) have been detected in patients with sporadic ALS, suggesting the importance of TAF15-PrLD in ALS pathogenesis. Herein, combining experiments and molecular dynamics (MD) simulations, we investigated the influences of several TAF15-PrLD mutations on the amyloid fibril formation of TAF15-PrLD-extracted peptide segments, and identified an essential β-amyloid-forming segment from TAF15-PrLD. A pathogenic mutation T2 E71G resulted in significantly enhanced aggregation of the TAF15-PrLD segment T2 (Y⁵⁶GQSQSGYSQSYGGYENQ⁷³). In addition, the peptide T2 with a strong β-amyloid-forming te

SUBMITTER: Chen J 

PROVIDER: S-EPMC9300678 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature