恶性疟原虫CSP蛋白重复序列对肝素结合的影响  

The Role of Repeat Region of Plasmodium falciparum Circumsporozoite Protein in Heparin Binding

作　　者：隋委伽 史小雨 Sui Weijia;Shi Xiaoyu(Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, Chin)

机构地区：[1]天津医科大学基础医学院免疫学系,天津300070

出　　处：《南开大学学报（自然科学版）》2018年第3期66-71,共6页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：天津市高等学校基本科研业务费资助项目(11601501/2016KJ0138)

摘　　要：疟疾是1种严重的传染性寄生虫病,其病原体为疟原虫,而子孢子(sporozoite)则是其传染性阶段.主要研究感染人体的恶性疟原虫(Plasmodium falciparum,Pf)的主要子孢子表面蛋白:环子孢子蛋白CSP(circumsporozoite protein).CSP可以识别肝细胞表面的硫酸乙酰软骨素(heparan sulfate proteoglycans,HSPGs),从而介导疟原虫子孢子对肝实质细胞的入侵,特异性识别CSP的抗体也是目前为止颇有希望的防疟手段.CSP由N端结构域,中央NANP重复序列(Central NANP Repeats)和C端的TSR(thrombospodin type-I repeat)结构域组成.前期研究显示,CSP中不同区域位点的缺失或突变对CSP结合肝实质细胞产生不同程度的影响,但中央NANP重复序列在肝素识别中的作用还不清楚.通过构建了缺失全部重复序列的CSP突变体,并进行突变体的纯化和肝素亲和实验,发现重复序列的缺失并不影响CSP蛋白的表达及与肝素的相互作用.这些结果为进一步研究CSP的结构和功能提供了理论依据.Malaria is one of the most deadly infectious disease. The pathogen of the disease is Plasmodium,and sporozoite is the contagious form. Here, this study focuses on the major surface protein of Plasmodium falciparum sporozoite： circumsporozoite protein（CSP）. CSP can recognize the heparan sulfate proteoglycans（HSPGs） on the surface of hepatocyte and initiate the invasion of liver. Antibodies against CSP fragments are the most promising anti-malaria tools so far. CSP is composed of a N-terminal domain, a central NANP repeat, and a C-terminal TSR domain. Previous studies have shown that interactions with heparin are affected by various mutations or deletions of CSP. However, the role of the CSP tandem repeat region in heparin binding remains elusive. In this study, a CSP mutant lacking the entire repeat region is constructed and purified. Heparin binding assay indicates that the CSP repeat region has no effect on CSP-heparin interaction. These results provide new evidences for further studies on the structure and function of CSP.

关 键 词：恶性疟原虫 环子孢子蛋白CSP 中央NANP重复序列 肝素 

分 类 号：R382.31[医药卫生—医学寄生虫学]