mHSP70分子中免疫刺激肽段与CD40对接复合物的结构模拟

Docking Analysis of Immune-Stimulating Peptide in mHSP70 with CD40 Complex

微生物体内的70 ku热休克蛋白407-426片段可以有效刺激体内CD40+抗原递呈细胞如DC,单核细胞等的成熟,可有效刺激体内产生IL12和TNFα,被认为是CD40L的替代配体,因此对免疫系统有着重要的意义。同时,该片段还可以有效结合外源蛋白分子,因此又是天然的递呈抗原的载体佐剂。该文章以开发新型载体佐剂为目的,使用Discovery studio软件分析经过单片段与两次串联的该肽段结构并预测了它们与CD40分子进行对接后的复合物。经过分析其关键结合位点,阐明了该肽段与CD40分子间参与相互作用的残基,并发现经过2次串联的肽段确实可以比单片段更有效的与CD40进行相互作用。因此,实验结果可为新型肿瘤疫苗的设计提供理论依据。

It is well known that the 70 ku microbial heat shock protein（mHSP70） has a profound effect on the immune system. In the year of 2005, a crucial cytokine-stimulating epitope （peptide 407-426 ） inside the mHSP70 was identified and highly praised for its function in interacting with the CD40 receptor on DCs and monocytes to produce cytokines and chemokine. It significantly enhanced the maturation of DCs. Thus it may serve as an alternative ligand to its nature binding molecule：CD154. This remarkable finding gives us an opportunity to design a novel antigen carrier adjuvant to compensate the shortcoming of our current vaccines＇ poor efficient in uptake and cross-presentation of Tumor Associated Antigens （TAAs） ,and the lacking immunogenicity as well. By using the function of Modeller, Molecular Dynamics and ZDock that embed in the software of Discovery studio, the homology model of none/double tandem repeats peptide has been built and the docking position between them and CD40 also studied to analyze the crucial binding sites in the interface of CD40-CD154. It was found that the double tandem repeats peptide had a better docking position to binding with C D40＇s crucial residues, and became more stabilized compared with single peptide. Thus, these results could be constructive for developing novel anti-tumor vaccines.