Amyloid-like aggregation of bovine serum albumin at physiological temperature induced by cross-seeding effect of HEWL amyloid aggregates

BSA can form amyloid-like aggregates in vitro at 65 degrees C. Heterologous amyloid can proposedly cross-seed other protein's aggregation, however, general mechanisms and driving conditions remain to be vividly elucidated. Here, we examined if pre-formed HEWL amyloid can cross-seed the aggregation of BSA at physiological temperature, 37 degrees C, and whether the efficacy depends on the BSA conformation. We find that at pH 3.0, 37 degrees C where BSA manifests exposure of abundant hydrophobic patches, HEWL amyloid efficiently drives BSA into ThTpositive, sarkosyl-resistant, beta-sheet rich amyloid-like aggregates exhibiting fibrils in TEM. On the contrary, HEWL amyloid fails to cross-seed the BSA aggregation at pH 7.0, 37 degrees C where BSA has largely internalized hydrophobic patches. Strikingly, human lysozyme amyloid could also cross-seed human serum albumin aggregation at pH 3.0, 37 degrees C. Thus, heterologous amyloid cross-seeding can help overcome the energy-barrier for aggregation of other proteins that, for any reason, may have perturbed and promiscuous structural conformation at physiological temperatures.

Automated summary

This study found that HEWL amyloid could efficiently drive BSA aggregation at pH 3.0, 37 degrees Celsius, but not at pH 7.0. Additionally, human lysozyme amyloid was also able to cross-seed human serum albumin aggregation under the same conditions.