The Study Of Selected Complexes Of Human Serum Albumin With Amyloid Beta Peptides And Human Cystatin C

Human serum albumin (HSA), due to its easy availability and specific properties, is probably one of the most studied proteins. Therefore it is also one of the most commonly used model proteins in biochemical laboratories. The physiological role of HSA is to bind and transport a number of hydrophobic molecules, such as fatty acids or steroids, in the human body. Albumin also binds metal ions and a number of drug molecules. It has also been observed that HSA is able to bind beta amyloid peptides, which may affect the formation process of amyloid deposits in Alzheimer's disease [1]. The aim of our research was to determine the structure of human plasma albumin complexes with selected amyloid beta peptides, in particular with Aβ peptides 1-42 and 3-28. Moreover, we started analysis of the structure of the triple complex HSA/Aβ 1-42 with human cystatin C (HCC). These complexes in the solution were analyzed using the methods based on scattering of synchrotron radiation and neutrons (SAXS/SANS) and dynamic light scattering (DLS). We have observed changes in the radii of gyration characterizing HSA/Aβ complexes, which indicates the compaction process of HSA molecule upon binding of Aβ peptide. In parallel, we analyzed the influence of HSA on the morphology of fibril deposits and Aβ peptide aggregates obtained under various in vitro conditions. We supplemented the experimental research with simulations of molecular dynamics of the structure of selected HSA/Aβ complexes. Acknowledgments: The study was supported by National Science Centre (Poland) - grant number 2017/27/B/ST4/00485.[1] Stanyon H.F., Viles J.H. J Biol Chem. 287 (2012) 28163-28168.