Department of Biochemistry, Eötvös Loránd University, 1117, Budapest, Hungary.
Department of Biochemistry, Semmelweis University, 1094, Budapest, Hungary.
Sci Rep. 2022 Apr 7;12(1):5904. doi: 10.1038/s41598-022-09574-2.
S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally occurring S100 partners in the human proteome. Such information will be precious for future drug design to interfere with S100 related pathologies.
S100 蛋白是小型的、通常为同源二聚体的脊椎动物特异性 EF 手蛋白，可在细胞内外环境中建立 Ca 依赖性蛋白-蛋白相互作用，并在各种病理情况下过度表达。人类中约有 20 种不同的 S100 蛋白，具有许多潜在的伴侣蛋白。在这里，我们使用定量滞留测定法测量了 S100 蛋白家族的大多数成员与化学合成的折叠体文库的亲和力谱。这些图谱使我们能够定量地绘制每个成员与折叠体文库的结合混杂性。由于该文库被设计为系统地包含大多数二元天然氨基酸侧链组合，因此数据还提供了对每个 S100 蛋白对人类蛋白质组中所有潜在天然 S100 伴侣的混杂性的深入了解。此类信息对于未来的药物设计以干扰与 S100 相关的病理将非常宝贵。
