Structural characterization of the interaction between the Alzheimer's disease beta-amyloid peptide and the catechin EGCG

• Applicant: Professor Dr. Bernd Reif
• Subject Area: Structural Biology ; Biophysics
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264855120

• Final Report Year: 2019

Final Report Abstract

We have shown that EGCG affects the solubility of aggregation prone peptides and proteins. We find that EGCG interacts stronger with those proteins which have a higher tendency to aggregate. This is presumably due to their decreased thermodynamic stability which in turn increases the likelihood of local unfolding events. MAS solid-state NMR experiments show that VL amyloid aggregates are well structured, but do not share a common fibrillary fold when compared to fibrils formed by other light chain amyloid sequences. Addition of EGCG induces amorphous aggregation, with only very little structural homogeneity left in the aggregated state. It remains to be seen which structural elements and which interactions are important for AL fibril structure, and how these interactions are exploited by EGCG.

Publications

• (2017) Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains. Sci Rep 7, e41515
  Hora M., Carballo-Pacheco M., Weber B., Morris V. K., Wittkopf A., Buchner J., Strodel B., Reif B.
  
• (2018) Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice. Sci Rep 8, article no. 1116
  Franko A., Rodriguez Camargo D. C., Böddrich A., Garg D., Rodriguez Camargo A., Rozman J., Rathkolb B., Janik D., Aichler M., Feuchtinger A., Neff F., Fuchs H., Wanker E. E., Reif B., Häring H.-U., Peter A., Hrabě de Angelis M.