Aggregation and fibrillation of bovine serum albumin.

@article{citeulike:1770772, 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.}, address = {Centre for Insoluble Protein Structures (inSPIN) at Department of Life Sciences, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark.}, author = {Holm, N. K. and Jespersen, S. K. and Thomassen, L. V. and Wolff, T. Y. and Sehgal, P. and Thomsen, L. A. and Christiansen, G. and Andersen, C. B. and Knudsen, A. D. and Otzen, D. E. }, citeulike-article-id = {1770772}, doi = {10.1016/j.bbapap.2007.06.008}, issn = {0006-3002}, journal = {Biochim Biophys Acta}, keywords = {amyloid, clip}, month = {September}, number = {9}, pages = {1128--1138}, posted-at = {2007-10-15 17:41:41}, priority = {2}, title = {Aggregation and fibrillation of bovine serum albumin.}, url = {http://dx.doi.org/10.1016/j.bbapap.2007.06.008}, volume = {1774}, year = {2007} }

TY - JOUR ID - citeulike:1770772 L3 - citeulike-article-id:1770772 TI - Aggregation and fibrillation of bovine serum albumin. JF - Biochim Biophys Acta VL - 1774 IS - 9 SP - 1128 EP - 1138 AD - Centre for Insoluble Protein Structures (inSPIN) at Department of Life Sciences, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark. SN - 0006-3002 N2 - 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. KW - amyloid KW - clip AU - Holm, NK AU - Jespersen, SK AU - Thomassen, LV AU - Wolff, TY AU - Sehgal, P AU - Thomsen, LA AU - Christiansen, G AU - Andersen, CB AU - Knudsen, AD AU - Otzen, DE PY - 2007/09// UR - http://dx.doi.org/10.1016/j.bbapap.2007.06.008 ER -