Yurkina Daria M, Shcherbakov Kirill A, Romanova Elena A, Tvorogova Anna V, Feoktistov Alexey M, Georgiev Georgii P, Yashin Denis V, Sashchenko Lidia P
Institute of Gene Biology (RAS), 119334 Moscow, Russia.
Institute of Molecular Biology (RAS), 119334 Moscow, Russia.
Int J Mol Sci. 2025 Apr 25;26(9):4069. doi: 10.3390/ijms26094069.
The pro-inflammatory immune response plays an important role in protecting the body from pathogens and tumors. In this study, we were able to identify three peptides of the innate immunity protein PGLYRP1 (Tag7) that could regulate the activity of the TREM-1 receptor. TREM-1 receptor activation on monocytes triggers the appearance of antitumor lymphocytes. All three peptides studied (17.0, N9, and N15) bind with the TREM-1 receptor with the Kds 1.32 ± 0.2 nM, 9.66 ± 0.5 nM, and 7.43 ± 0.4 nM, respectively. An N9 peptide inhibiting the activity of the receptor was identified in addition to two peptides (N9 and N15) that jointly trigger the activation of the receptor. The conducted molecular docking study revealed amino acid residues (Ile57, Ile58, Glu106, Ser108, Leu110, Tyr116, Pro118, Pro119, Arg130, and Val 132), necessary for various functions of peptides, providing important knowledge for understanding the mechanism of activation of this receptor that can also serve as a basis for the development of therapeutic drugs to regulate its activity in the treatment of autoimmune diseases and tumors.
促炎免疫反应在保护机体免受病原体和肿瘤侵害方面发挥着重要作用。在本研究中，我们能够鉴定出天然免疫蛋白PGLYRP1（Tag7）的三种肽段，它们可以调节TREM-1受体的活性。单核细胞上TREM-1受体的激活会触发抗肿瘤淋巴细胞的出现。所研究的所有三种肽段（17.0、N9和N15）与TREM-1受体结合的解离常数（Kd）分别为1.32±0.2 nM、9.66±0.5 nM和7.43±0.4 nM。除了两种共同触发受体激活的肽段（N9和N15）外，还鉴定出了一种抑制受体活性的N9肽段。进行的分子对接研究揭示了肽段各种功能所必需的氨基酸残基（Ile57、Ile58、Glu106、Ser108、Leu110、Tyr116、Pro118、Pro119、Arg130和Val 132），为理解该受体的激活机制提供了重要知识，这也可为开发调节其活性以治疗自身免疫性疾病和肿瘤的治疗药物奠定基础。
