Biomolecules, Vol. 15, Pages 431: Binding of Pro-inflammatory Proteins S100A8 or S100A9 to Amyloid-β Peptide Suppresses Its Fibrillation

Biomolecules doi: 10.3390/biom15030431

Authors:
Ekaterina A. Litus
Marina P. Shevelyova
Alisa A. Vologzhannikova
Evgenia I. Deryusheva
Andrey V. Machulin
Ekaterina L. Nemashkalova
Maria E. Permyakova
Andrey S. Sokolov
Valeria D. Alikova
Vladimir N. Uversky
Sergei E. Permyakov

Human serum albumin (HSA) is a natural depot of amyloid-β peptide (Aβ), a key player in Alzheimer’s disease (AD). HSA and pro-inflammatory Ca2+-binding proteins S100A8 and S100A9 are involved in Aβ metabolism and its deposition in the brain, serving as probable triggers and therapeutic targets in AD, but their interplay with regard to Aβ binding/fibrillation is unclear. To this end, here we explore the in vitro binding of Ca2+-bound S100A8 or S100A9 to monomeric Aβ and the influence of the S100 proteins on Aβ fibrillation. The equilibrium dissociation constants of the complexes of dimeric S100A8/S100A9 with Aβ40/42 estimated by biolayer interferometry are 1–5 µM. S100A8 and S100A9 interfere with HSA binding to Aβ. Thioflavin T assay and electron microscopy data show that micromolar S100A8/S100A9 inhibit Aβ40 fibrillation, and the inhibitory effect of S100A8 exceeds that for HSA. The competition for Aβ between HSA and S100A8/S100A9 may contribute to the Aβ-HSA imbalance in the pro-inflammatory conditions in AD.

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Ekaterina A. Litus www.mdpi.com