Aggregation and fibrillation of bovine serum albumin

Biochim Biophys Acta. 2007 Sep;1774(9):1128-38. doi: 10.1016/j.bbapap.2007.06.008. Epub 2007 Jul 6.

Abstract

The all-alpha helix multi-domain protein bovine serum albumin (BSA) aggregates at elevated temperatures. Here we show that these thermal aggregates have amyloid properties. They bind the fibril-specific dyes Thioflavin T and Congo Red, show elongated although somewhat worm-like morphology and characteristic amyloid X-ray fiber diffraction peaks. Fibrillation occurs over minutes to hours without a lag phase, is independent of seeding and shows only moderate concentration dependence, suggesting intramolecular aggregation nuclei. Nevertheless, multi-exponential increases in dye-binding signal and changes in morphology suggest the existence of different aggregate species. Although beta-sheet content increases from 0 to ca. 40% upon aggregation, the aggregates retain significant amounts of alpha-helix structure, and lack a protease-resistant core. Thus BSA is able to form well-ordered beta-sheet rich aggregates which nevertheless do not possess the same structural rigidity as classical fibrils. The aggregates do not permeabilize synthetic membranes and are not cytotoxic. The ease with which a multidomain all-alpha helix protein can form higher-order beta-sheet structure, while retaining significant amounts of alpha-helix, highlights the universality of the fibrillation mechanism. However, the presence of non-beta-sheet structure may influence the final fibrillar structure and could be a key component in aggregated BSA's lack of cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / ultrastructure*
  • Animals
  • Benzothiazoles
  • Cattle
  • Cell Survival
  • Congo Red / chemistry
  • Neuroblastoma
  • Protein Structure, Secondary
  • Serum Albumin, Bovine / chemistry*
  • Serum Albumin, Bovine / ultrastructure*
  • Spectroscopy, Fourier Transform Infrared
  • Thiazoles / chemistry
  • Trypsin / metabolism
  • Tumor Cells, Cultured
  • X-Ray Diffraction

Substances

  • Amyloid
  • Benzothiazoles
  • Thiazoles
  • thioflavin T
  • Serum Albumin, Bovine
  • Congo Red
  • Trypsin