入侵宿主红细胞是疟疾的疟原虫的病理和发展必不可少的生命周期。红细胞浸润的阶段，包括最初的接触，根尖定位，结的形成，和积极的内陷，是由专门的根尖细胞器和它们的寄生虫蛋白内容协调释放。在这些蛋白，和所有物种的中央的侵袭，是两个寄生虫的蛋白质家族，网织红细胞结合蛋白的同源性（RH）和红细胞结合蛋白，它介导的宿主–寄生虫interactions2。5从恶性疟原虫（pfrh5）是家庭成员中唯一证明在所有测试的菌株细胞侵袭是必要的，通过与红细胞表面蛋白Basigin的相互作用（也称为CD147和EMMPRIN）3，4。针对pfrh5或其有效地阻止寄生虫侵袭vitro4，5，6，7，8，9的抗体，使pfrh5极好的候选疫苗。在这里，我们目前的晶体结构的pfrh5与Basigin和两个不同的抑制性抗体复合物。pfrh5采用了新的折叠二三螺旋束在一起的风筝一样的结构，提出了其抑制抗体结合位点在一个提示。这提供了第一个结构洞察疟原虫红细胞结合的Rh蛋白家族和确定新的抑制抗原表位指导对血液阶段寄生虫疫苗的新一代设计。
原文：
Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies
Katherine E. Wright,Kathryn A. Hjerrild,Jonathan Bartlett,Alexander D. Douglas, Jing Jin, Rebecca E. Brown,Joseph J. Illingworth, Rebecca Ashfield,Stine B. Clemmensen, Willem A. de Jongh, Simon J. Draper & Matthew K. Higgins
Invasion of host erythrocytes is essential to the life cycle of Plasmodium parasites and development of the pathology of malaria. The stages of erythrocyte invasion, including initial contact, apical reorientation, junction formation, and active invagination, are directed by coordinated release of specialized apical organelles and their parasite protein contents1. Among these proteins, and central to invasion by all species, are two parasite protein families, the reticulocyte-binding protein homologue (RH) and erythrocyte-binding like proteins, which mediate host–parasite interactions2. RH5 from Plasmodium falciparum (PfRH5) is the only member of either family demonstrated to be necessary for erythrocyte invasion in all tested strains, through its interaction with the erythrocyte surface protein basigin (also known as CD147 and EMMPRIN)3, 4. Antibodies targeting PfRH5 or basigin efficiently block parasite invasion in vitro4, 5, 6, 7, 8, 9, making PfRH5 an excellent vaccine candidate. Here we present crystal structures of PfRH5 in complex with basigin and two distinct inhibitory antibodies. PfRH5 adopts a novel fold in which two three-helical bundles come together in a kite-like architecture, presenting binding sites for basigin and inhibitory antibodies at one tip. This provides the first structural insight into erythrocyte binding by the Plasmodium RH protein family and identifies novel inhibitory epitopes to guide design of a new generation of vaccines against the blood-stage parasite.
