Chitnis C E, Miller L H
Laboratory of Malaria Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1994 Aug 1;180(2):497-506. doi: 10.1084/jem.180.2.497.
Plasmodium vivax and the related monkey malaria, P. knowlesi, require interaction with the Duffy blood group antigen, a receptor for a family of chemokines that includes interleukin 8, to invade human erythrocytes. One P. vivax and three P. knowlesi proteins that serve as erythrocyte binding ligands in such interactions share sequence homology. Expression of different regions of the P. vivax protein in COS7 cells identified a cysteine-rich domain that bound Duffy blood group-positive but not Duffy blood group-negative human erythrocytes. The homologous domain of the P. knowlesi proteins also bound erythrocytes, but had different specificities. The P. vivax and P. knowlesi binding domains lie in one of two regions of homology with the P. falciparum sialic acid binding protein, another erythrocyte binding ligand, indicating conservation of the domain for erythrocyte binding in evolutionarily distant malaria species. The binding domains of these malaria ligands represent potential vaccine candidates and targets for receptor-blockade therapy.
间日疟原虫及相关的猴疟原虫——诺氏疟原虫，需要与达菲血型抗原相互作用才能侵入人类红细胞，达菲血型抗原是包括白细胞介素8在内的一类趋化因子的受体。在这种相互作用中作为红细胞结合配体的一种间日疟原虫蛋白和三种诺氏疟原虫蛋白具有序列同源性。在COS7细胞中表达间日疟原虫蛋白的不同区域，鉴定出一个富含半胱氨酸的结构域，该结构域能结合达菲血型阳性而非达菲血型阴性的人类红细胞。诺氏疟原虫蛋白的同源结构域也能结合红细胞，但具有不同的特异性。间日疟原虫和诺氏疟原虫的结合结构域位于与恶性疟原虫唾液酸结合蛋白（另一种红细胞结合配体）的两个同源区域之一，这表明在进化上距离较远的疟原虫物种中，红细胞结合结构域具有保守性。这些疟疾配体的结合结构域代表了潜在的疫苗候选物和受体阻断疗法的靶点。
