| Title |
Calcium-dependent S100A8 amyloid fibril formation via S100A1-mediated transient interaction |
| Authors |
Karalkevičiūtė, Viktorija ; Baronaitė, Ieva ; Peštenytė, Aistė ; Veiveris, Dominykas ; Usevičius, Gediminas ; Šimėnas, Mantas ; Žiaunys, Mantas ; Smirnovas, Vytautas ; Šulskis, Darius |
| DOI |
10.1021/acschemneuro.5c00086 |
| Full Text |
|
| Is Part of |
ACS Chemical neuroscience.. Washington : American Chemical Society. 2025, vol. 16, iss. 14, p. 2592-2601.. eISSN 1948-7193 |
| Keywords [eng] |
aggregation ; amyloid ; inflammation ; interaction ; neurodegeneration ; S100 |
| Abstract [eng] |
The S100 family consists of calcium-binding proteins that are largely known for their contribution to neuroinflammatory processes. These proteins are associated with various cardiac and neurological functions as well as related diseases. A few S100 proteins can form unspecific or amyloid aggregates in neuropathologies and thus play a part in dementia pathogenesis. Among all S100 proteins, S100B and S100A9 aggregation properties are the most investigated; however, there is a lack of studies regarding other S100 members. In particular, S100A1 and S100A8 are also associated with neurological pathologies, but their interactions and aggregation are poorly understood. Therefore, in this study, we explored whether S100A1 and S100A8 proteins can form heterodimers, interact, or coaggregate. Our results revealed that S100A1 and S100A8 interactions and S100A8 amyloid aggregation are driven by calcium ions. We observed that while S100A1 remains mostly stable, S100A8 forms various types of spherical or unspecific aggregates. While they do not form stable heterodimers like calprotectin, their transient interactions facilitate the formation of worm-like amyloid fibrils, and the process is regulated by different calcium ion concentrations. At calcium ion saturation, both proteins are stabilized, leading to inhibition of aggregation. Overall, by employing a diverse range of techniques from amyloid and protein-specific fluorescence detection to electron-electron double resonance spectroscopy, we elucidated interactions between S100 proteins that might otherwise be overlooked, enhancing our understanding of their aggregation behavior. |
| Published |
Washington : American Chemical Society |
| Type |
Journal article |
| Language |
English |
| Publication date |
2025 |
| CC license |
|
