Université Paris Cité and CNRS, ITDODYS, F-75006, Paris, France.
Université de Lorraine and CNRS, UMR 7053L2CM, F-54000, Nancy, France.
Chemistry. 2024 Apr 16;30(22):e202304318. doi: 10.1002/chem.202304318. Epub 2024 Feb 28.
T cell transmembrane, Immunoglobulin, and Mucin (TIM) are important immune system proteins which are especially present in T-cells and regulated the immune system by sensing cell engulfment and apoptotic processes. Their role is exerted by the capacity to detect the presence of phosphatidyl-serine lipid polar head in the outer leaflet of cellular membranes (correlated with apoptosis). In this contribution by using equilibrium and enhanced sampling molecular dynamics simulation we unravel the molecular bases and the thermodynamics of TIM, and in particular TIM-3, interaction with phosphatidyl serine in a lipid bilayer. Since TIM-3 deregulation is an important factor of pro-oncogenic tumor micro-environment understanding its functioning at a molecular level may pave the way to the development of original immunotherapeutic approaches.
T 细胞跨膜蛋白、免疫球蛋白和粘蛋白（TIM）是重要的免疫系统蛋白，它们特别存在于 T 细胞中，并通过感应细胞吞噬和凋亡过程来调节免疫系统。它们的作用是通过检测细胞膜外层磷脂酰丝氨酸脂质极性头的存在来发挥的（与凋亡相关）。在本研究中，我们使用平衡和增强采样分子动力学模拟来揭示 TIM，特别是 TIM-3 与双层脂质中的磷脂酰丝氨酸相互作用的分子基础和热力学。由于 TIM-3 的失调是致癌肿瘤微环境的重要因素，因此了解其在分子水平上的功能可能为开发原创免疫治疗方法铺平道路。
