Goel Vikas K, Li Xuerong, Chen Huiqing, Liu Shih-Chun, Chishti Athar H, Oh Steven S
Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5164-9. doi: 10.1073/pnas.0834959100. Epub 2003 Apr 11.
We report the molecular identification of a sialic acid-independent host-parasite interaction in the Plasmodium falciparum malaria parasite invasion of RBCs. Two nonglycosylated exofacial regions of human band 3 in the RBC membrane were identified as a crucial host receptor binding the C-terminal processing products of merozoite surface protein 1 (MSP1). Peptides derived from the receptor region of band 3 inhibited the invasion of RBCs by P. falciparum. A major segment of the band 3 receptor (5ABC) bound to native MSP1(42) and blocked the interaction of native MSP1(42) with intact RBCs in vitro. Recombinant MSP1(19) (the C-terminal domain of MSP1(42)) bound to 5ABC as well as RBCs. The binding of both native MSP1(42) and recombinant MSP1(19) was not affected by the neuraminidase treatment of RBCs, but sensitive to chymotrypsin treatment. In addition, recombinant MSP1(38) showed similar interactions with the band 3 receptor and RBCs, although the interaction was relatively weak. These findings suggest that the chymotrypsin-sensitive MSP1-band 3 interaction plays a role in a sialic acid-independent invasion pathway and reveal the function of MSP1 in the Plasmodium invasion of RBCs.
我们报告了恶性疟原虫入侵红细胞过程中一种不依赖唾液酸的宿主-寄生虫相互作用的分子鉴定。红细胞膜上人类带3蛋白的两个非糖基化细胞外区域被确定为与裂殖子表面蛋白1(MSP1)的C端加工产物结合的关键宿主受体。源自带3蛋白受体区域的肽可抑制恶性疟原虫对红细胞的入侵。带3蛋白受体的一个主要片段(5ABC)与天然MSP1(42)结合,并在体外阻断天然MSP1(42)与完整红细胞的相互作用。重组MSP1(19)(MSP1(42)的C端结构域)与5ABC以及红细胞结合。天然MSP1(42)和重组MSP1(19)的结合不受红细胞神经氨酸酶处理的影响,但对胰凝乳蛋白酶处理敏感。此外,重组MSP1(38)与带3蛋白受体和红细胞表现出相似的相互作用,尽管这种相互作用相对较弱。这些发现表明,对胰凝乳蛋白酶敏感的MSP1-带3蛋白相互作用在不依赖唾液酸的入侵途径中起作用,并揭示了MSP1在疟原虫入侵红细胞中的功能。