Department of Bioinformatics and Chemical Communication (D-BICC), Research Institute in Semiochemistry and Applied Ethology (IRSEA), Quartier Salignan, 84400 Apt, France.
Research and Education Board, Research Institute in Semiochemistry and Applied Ethology (IRSEA), Quartier Salignan, 84400 Apt, France.
Int J Mol Sci. 2023 Jul 20;24(14):11685. doi: 10.3390/ijms241411685.
The major cat allergen Fel d 1 is a tetrameric glycoprotein from the secretoglobin superfamily. Fel d 1's biological role is unknown, but it has been previously shown that it participates in semiochemical binding/transportation. Fel d 1 has linear epitopes, but its conformational epitope sites remain unclear. In this study, we predicted the B-cell epitopes of Fel d 1 and explored semiochemical dynamics with epitopes using bioinformatics tools. The epitope residues were tabulated for chains 1 and 2 and the heterodimers of Fel d 1. The residual interactions of Fel d 1 with IgE were evaluated, and the prominent epitope sites were predicted. The molecular dynamics simulation (MDS) of Fel d 1 was performed with seven reported semiochemicals to evaluate the Fel d 1-ligand complex stability and decipher the semiochemical effect on Fel d 1 conformational epitopes. Fel d 1-lauric acid, Fel d 1-oleic acid, and Fel d 1-progesterone showed more stability and less fluctuation than other compounds. Fel d 1-linoleic acid and Fel d 1-pregnenolone displayed the most unstable complex with fluctuations. The effects of conformational changes on epitopes are discussed. All the ligand complexes drive substantial fluctuation towards the functionally exposed IgE-binding epitopes. Fel d 1 could be examined for its ligand-binding and conformational changes caused by mutations of B-cell epitopes.
主要的猫过敏原 Fel d 1 是来自 secretoglobin 超家族的四聚体糖蛋白。Fel d 1 的生物学作用尚不清楚，但先前已经表明它参与了信息素结合/运输。Fel d 1 具有线性表位，但它的构象表位位点仍不清楚。在这项研究中，我们预测了 Fel d 1 的 B 细胞表位，并使用生物信息学工具探索了表位的半化学动力学。表位残基被列于 Fel d 1 的链 1 和 2 以及异二聚体中。评估了 Fel d 1 与 IgE 的剩余相互作用，并预测了突出的表位位点。对 Fel d 1 与七种报道的半化学物质进行了分子动力学模拟 (MDS)，以评估 Fel d 1-配体复合物的稳定性，并破译半化学物质对 Fel d 1 构象表位的影响。与其他化合物相比，Fel d 1-月桂酸、Fel d 1-油酸和 Fel d 1-孕酮表现出更高的稳定性和更少的波动。Fel d 1-亚油酸和 Fel d 1-孕烯醇酮与最不稳定的复合物显示出波动。讨论了构象变化对表位的影响。所有配体复合物都导致功能暴露的 IgE 结合表位发生大量波动。可以检查 Fel d 1 配体结合和 B 细胞表位突变引起的构象变化。
