| Title |
Formation of calprotectin inhibits amyloid aggregation of S100A8 and S100A9 proteins / |
| Authors |
Baronaitė, Ieva ; Šulskis, Darius ; Kopūstas, Aurimas ; Tutkus, Marijonas ; Smirnovas, Vytautas |
| DOI |
10.1021/acschemneuro.4c00093 |
| Full Text |
|
| Is Part of |
ACS Chemical Neuroscience.. Washington : American Chemical Society. 2024, vol. 15, iss. 9, p. 1915-1925.. eISSN 1948-7193 |
| Keywords [eng] |
aggregation ; amyloid ; inflammation ; S100 |
| Abstract [eng] |
Calcium-binding S100A8 and S100A9 proteins play a significant role in various disorders due to their pro-inflammatory functions. Substantially, they are also relevant in neurodegenerative disorders via the delivery of signals for the immune response. However, at the same time, they can aggregate and accelerate the progression of diseases. Natively, S100A8 and S100A9 exist as homo- and heterodimers, but upon aggregation, they form amyloid-like oligomers, fibrils, or amorphous aggregates. In this study, we aimed to elucidate the aggregation propensities of S100A8, S100A9, and their heterodimer calprotectin by investigating aggregation kinetics, secondary structures, and morphologies of the aggregates. For the first time, we followed the in vitro aggregation of S100A8, which formed spherical aggregates, unlike the fibrillar structures of S100A9 under the same conditions. The aggregates were sensitive to amyloid-specific ThT and ThS dyes and had a secondary structure composed of β-sheets. Similarly to S100A9, S100A8 protein was stabilized by calcium ions, resulting in aggregation inhibition. Finally, the formation of S100A8 and S100A9 heterodimers stabilized the proteins in the absence of calcium ions and prevented their aggregation. |
| Published |
Washington : American Chemical Society |
| Type |
Journal article |
| Language |
English |
| Publication date |
2024 |
| CC license |
|
