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.

中文翻译：

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钙卫蛋白的形成抑制 S100A8 和 S100A9 蛋白的淀粉样蛋白聚集

钙结合 S100A8 和 S100A9 蛋白因其促炎功能而在多种疾病中发挥重要作用。实质上，它们还通过传递免疫反应信号与神经退行性疾病相关。然而，与此同时，它们可以聚集并加速疾病的进展。天然情况下，S100A8 和 S100A9 以同二聚体和异二聚体形式存在，但在聚集后，它们形成淀粉样蛋白样寡聚体、原纤维或无定形聚集体。在本研究中，我们旨在通过研究聚集体的聚集动力学、二级结构和形态来阐明 S100A8、S100A9 及其异二聚体钙卫蛋白的聚集倾向。我们首次跟踪了S100A8的体外聚集，其形成球形聚集体，与相同条件下S100A9的纤维状结构不同。该聚集体对淀粉样蛋白特异性 ThT 和 ThS 染料敏感，并具有由 β-折叠组成的二级结构。与S100A9类似，S100A8蛋白被钙离子稳定，从而抑制聚集。最后，S100A8 和 S100A9 异二聚体的形成在没有钙离子的情况下稳定了蛋白质并防止其聚集。