死亡受体5氨基末端的结构与功能

Structural and Functional Analysis of the N-terminal Region of Death Receptor 5

目的研究死亡受体5(DR5)氨基末端的结构与功能。方法利用基因工程技术构建一系列DR5胞外区(DR5-ECD)缺失突变体并获得相应的重组蛋白。利用蛋白免疫印迹及ELISA技术研究重组蛋白与小鼠抗人DR5单克隆抗体AD5-10的结合情况。结果含有完整氨基末端结构的DR5-ECD缺失突变体能够与AD5-10结合,而缺失氨基末端的重组蛋白则不能与AD5-10相互作用。结论 DR5氨基末端含有AD5-10激动性抗体的靶点,该靶点可能在发展肿瘤免疫治疗新策略中发挥重要作用。

Objective To investigate the structure and function of the N-terminal region（NTR） of death receptor 5（DR5）.Methods A series of deletions of the DR5 extracellular domain（DR5-ECD） proteins were expressed in E.coli.and purified by affinity chromatography.The binding ability of these deletant proteins to AD5-10,a mouse anti-human DR5 monoclonal antibody,was evaluated by immunoblotting and ELISA.Results Recombinant DR5-ECD proteins containing the NTR were recognized and bound by AD5-10,while the other deletant proteins without the NTR failed to interact with AD5-10.Conclusion There is an AD5-10 targeting site in the NTR of DR5,which may play a role in developing novel immunotherapies for cancers.