Fibril structures of TFG protein mutants validate the identification of TFG as a disease-related amyloid protein by the IMPAcT method.

ABSTRACT: We previously presented a bioinformatic method for identifying diseases that arise from a mutation in a protein's low-complexity domain that drives the protein into pathogenic amyloid fibrils. One protein so identified was the tropomyosin-receptor kinase-fused gene protein (TRK-fused gene protein or TFG). Mutations in TFG are associated with degenerative neurological conditions. Here, we present experimental evidence that confirms our prediction that these conditions are amyloid-related. We find that the low-complexity domain of TFG containing the disease-related mutations G269V or P285L forms amyloid fibrils, and we determine their structures using cryo-electron microscopy (cryo-EM). These structures are unmistakably amyloid in nature and confirm the propensity of the mutant TFG low-compl

SUBMITTER: Rosenberg GM 

PROVIDER: S-EPMC10703350 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature