Uncovering the pathological functions of Ser404 phosphorylation by semisynthesis of a phosphorylated TDP-43 prion-like domain

Chem Commun (Camb). 2020 May 18;56(40):5370-5373. doi: 10.1039/d0cc01409e. Epub 2020 Apr 13.

Abstract

Herein, we have successfully semi-synthesized a TDP-43 prion-like domain with Ser404 phosphorylation. We have demonstrated that Ser404 phosphorylation could accelerate the amyloid aggregation of the TDP-43 prion-like domain and aggravate its cytotoxicity.

MeSH terms

  • Amyloidogenic Proteins / chemical synthesis
  • Amyloidogenic Proteins / metabolism
  • Amyloidogenic Proteins / pharmacology*
  • Amyloidogenic Proteins / toxicity
  • Animals
  • Cell Line, Tumor
  • DNA-Binding Proteins / chemical synthesis
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / pharmacology*
  • DNA-Binding Proteins / toxicity
  • Mice
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / toxicity
  • Phosphorylation
  • Prion Proteins / chemical synthesis
  • Prion Proteins / metabolism
  • Prion Proteins / pharmacology*
  • Prion Proteins / toxicity
  • Protein Domains
  • Protein Multimerization
  • Serine / chemistry*

Substances

  • Amyloidogenic Proteins
  • DNA-Binding Proteins
  • Peptide Fragments
  • Prion Proteins
  • Serine