Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes
Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes
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DOI：
10.7554/elife.04187
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发表时间：
2014-10-08
期刊：
影响因子：
7.7
通讯作者：
Cowman, Alan F.
中科院分区：
文献类型：
--
作者：
Chen, Lin;Xu, Yibin;Cowman, Alan F.
恶性疟原虫导致人类最严重的疟疾形式，每年造成超过70万人死亡。它是一种专性的细胞内寄生虫，入侵红细胞，生长在相对受保护的利基环境中。红细胞的入侵对寄生虫的生存至关重要，这涉及到多种蛋白质-蛋白质相互作用的相互作用。其中最重要的相互作用之一是寄生虫入侵配体家族EBLS和PfRh与红细胞表面的宿主受体结合。PfRh5是PfRh家族中唯一重要的侵袭配体，也是重要的候选疫苗。PfRh5与宿主受体basigin结合。在这里，我们用2.18A分辨率的衍射数据确定了PfRh5的晶体结构。PfRh5展示了一种新颖的折叠结构，该折叠结构由九个大部分反向平行的α-螺旋组成，包裹着一个N-末端的0-发夹，整体形状为椭圆盘。这是第一次确定PfRh蛋白家族的三维结构。
Plasmodium falciparum causes the most severe form of malaria in humans and is responsible for over 700,000 deaths annually. It is an obligate intracellular parasite and invades erythrocytes where it grows in a relatively protected niche. Invasion of erythrocytes is essential for parasite survival and this involves interplay of multiple protein-protein interactions. One of the most important interactions is binding of parasite invasion ligand families EBLs and PfRhs to host receptors on the surface of erythrocytes. PfRh5 is the only essential invasion ligand within the PfRh family and is an important vaccine candidate. PfRh5 binds the host receptor basigin. Here we have determined the crystal structure of PfRh5 using diffraction data to 2.18 A resolution. PfRh5 exhibits a novel fold comprising nine mostly-antiparallel a-helices encasing a N-terminal 0-hairpin, with the overall shape being an elliptical disk. This is the first three-dimensional structure determined for the PfRh family of proteins.