Structural Basis for the Immunomodulatory Function of Cysteine Protease Inhibitor from Human Roundworm Ascaris Iumbricoides
Immunosuppression associated with infections of nematode parasites has been documented.Cysteine protease inhibitor (CPI) released by the nematode parasites is identified as one of the major modulators of host immune response.In this report, we demonstrated that the recombinant CPI protein of Ascaris lumbricoides (AI-CPI) strongly inhibited the activities of cathepsin L, C, S, and showed weaker effect to cathepsin B.Crystal structure of AI-CPI was determined to 2.1 (A) resolution.Two segments of AI-CPI, loop 1 and loop 2, were proposed as the key structure motifs responsible for AI-CPI binding with proteases and its inhibitory activity.Mutations at loop 1 and loop 2 abrogated the protease inhibition activity to various extents.These results provide the molecular insight into the interaction between the nematode parasite and its host and will facilitate the development of anthelmintic agents or design of anti-autoimmune disease drugs.
Guoqiang Mei Jianmei Dong Zhaotao Li Sanling Liu Yunfeng Liu Mingze Sun Guiyun Liu Zhong Su Jinsong Liu
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese
国内会议
苏州
英文
380-388
2014-10-26（万方平台首次上网日期，不代表论文的发表时间）