McCutchan T F, Kissinger J C, Touray M G, Rogers M J, Li J, Sullivan M, Braga E M, Krettli A U, Miller L H
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA.
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11889-94. doi: 10.1073/pnas.93.21.11889.
The circumsporozoite (CS) protein of malaria parasites (Plasmodium) covers the surface of sporozoites that invade hepatocytes in mammalian hosts and macrophages in avian hosts. CS genes have been characterized from many Plasmodium that infect mammals; two domains of the corresponding proteins, identified initially by their conservation (region I and region II), have been implicated in binding to hepatocytes. The CS gene from the avian parasite Plasmodium gallinaceum was characterized to compare these functional domains to those of mammalian Plasmodium and for the study of Plasmodium evolution. The P. gallinaceum protein has the characteristics of CS proteins, including a secretory signal sequence, central repeat region, regions of charged amino acids, and an anchor sequence. Comparison with CS signal sequences reveals four distinct groupings, with P. gallinaceum most closely related to the human malaria Plasmodium falciparum. The 5-amino acid sequence designated region I, which is identical in all mammalian CS and implicated in hepatocyte invasion, is different in the avian protein. The P. gallinaceum repeat region consists of 9-amino acid repeats with the consensus sequence QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which is associated with targeting the invasion of liver cells, is also conserved in the avian protein. Phylogenetic analysis of the aligned Plasmodium CS sequences yields a tree with a topology similar to the one obtained using sequence data from the small subunit rRNA gene. The phylogeny using the CS gene supports the proposal that the human malaria P. falciparum is significantly more related to avian parasites than to other parasites infecting mammals, although the biology of sporozoite invasion is different between the avian and mammalian species.
疟原虫的环子孢子蛋白（CS）覆盖在子孢子表面，这些子孢子会侵入哺乳动物宿主的肝细胞以及禽类宿主的巨噬细胞。已经从许多感染哺乳动物的疟原虫中鉴定出了CS基因；相应蛋白质的两个结构域最初因其保守性而被确定（区域I和区域II），它们与结合肝细胞有关。对禽类疟原虫鸡疟原虫的CS基因进行了鉴定，以便将这些功能结构域与哺乳动物疟原虫的功能结构域进行比较，并用于疟原虫进化的研究。鸡疟原虫蛋白具有CS蛋白的特征，包括分泌信号序列、中央重复区域、带电荷氨基酸区域和锚定序列。与CS信号序列的比较揭示了四个不同的分组，鸡疟原虫与人类疟原虫恶性疟原虫关系最为密切。在所有哺乳动物CS中相同且与肝细胞入侵有关的5个氨基酸序列区域I，在禽类蛋白中有所不同。鸡疟原虫的重复区域由9个氨基酸的重复序列组成，共有序列为QP(A/V)GGNGG(A/V)。与靶向肝细胞入侵相关的保守基序区域II-plus在禽类蛋白中也保守。对排列后的疟原虫CS序列进行系统发育分析，得到的一棵树的拓扑结构与使用小亚基rRNA基因的序列数据得到的拓扑结构相似。使用CS基因的系统发育支持这样的观点，即人类疟原虫恶性疟原虫与禽类寄生虫的关系比与其他感染哺乳动物的寄生虫的关系更为密切，尽管禽类和哺乳动物物种的子孢子入侵生物学不同。
