Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane.
Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane.
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DOI：
10.1016/j.bbamem.2013.09.014
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发表时间：
2014-01
影响因子：
3.4
通讯作者：
An, Xiuli
中科院分区：
文献类型：
--
作者：
Weng, Haibo;Guo, Xinhua;Papoin, Julien;Wang, Jie;Coppel, Ross;Mohandas, Narla;An, Xiuli
恶性疟原虫在其生命周期的无性红细胞内阶段向红细胞质中输出大量蛋白质。这些蛋白质的一个子集与红细胞膜骨架蛋白相互作用，并严重改变膜的结构和功能。几种输出的蛋白质，如PfEMP 1，PfEMP 3，RESA和KAHRP，与优势的红细胞骨架蛋白血影蛋白相互作用。在这里，我们寻找了这四种疟疾蛋白与另一种主要的红细胞骨架蛋白锚蛋白R的可能相互作用。我们已经证明，KAHRP，但没有其他三个，结合锚蛋白R。我们已经映射了锚蛋白R的结合位点的79个残基的KAHRP序列的片段，和相互结合位点的KAHRP在锚蛋白R的一个子域（D3）的89 kDa的锚蛋白R膜结合结构域。完整的锚蛋白R与KAHRP的相互作用被抑制的自由D3亚结构域。此外，当装载有可溶性D3亚结构域的红细胞感染恶性疟原虫时，红细胞内寄生虫分泌的KAHRP不再迁移到宿主细胞膜，而是在整个胞质溶胶中弥散分布。我们的研究结果表明，KAHRP与红细胞膜骨架的相互作用，在促进疟疾感染的红细胞粘附到内皮细胞表面，疟疾的病理生理学中的一个核心要素，具有潜在的重要作用。
The malaria parasite Plasmodium falciparum exports a large number of proteins into the erythrocyte cytoplasm during the asexual intraerythrocytic stage of its life cycle. A subset of these proteins interacts with erythrocyte membrane skeletal proteins and grossly alters the structure and function of the membrane. Several of the exported proteins, such as PfEMP1, PfEMP3, RESA and KAHRP, interact with the preponderant erythrocyte skeleton protein, spectrin. Here we have searched for possible interaction of these four malaria proteins with another major erythrocyte skeleton protein, ankyrin R. We have shown that KAHRP, but none of the other three, binds to ankyrin R. We have mapped the binding site for ankyrin R to a 79-residue segment of the KAHRP sequence, and the reciprocal binding site for KAHRP in ankyrin R to a subdomain (D3) of the 89 kDa ankyrin R membrane-binding domain. Interaction of intact ankyrin R with KAHRP was inhibited by the free D3 subdomain. When, moreover, red cells loaded with the soluble D3 subdomain were infected with P. falciparum, KAHRP secreted by the intraerythrocytic parasite no longer migrated to the host cell membrane, but remained diffusely distributed throughout the cytosol. Our findings suggest a potentially important role for interaction of KAHRP with red cell membrane skeleton in promoting the adhesion of malaria-infected red cells to endothelial surfaces, a central element in the pathophysiology of malaria.
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旋钮阳性和旋钮阴性疟原虫恶性疟原虫在感染红细胞表面的菌株特异性疟疾抗原的表达上有所不同。
影响因子：
15.3
作者：
Aley, S B;Sherwood, J A;Howard, R J
通讯作者：
Howard, R J
影响因子：
1.5
作者：
Black, Casilda G.;Proellocks, Nicholas I.;Coppel, Ross L.
通讯作者：
Coppel, Ross L.
影响因子：
7.8
作者：
KENNEDY, SP;WARREN, SL;MORROW, JS
通讯作者：
MORROW, JS
影响因子：
20.3
作者：
Chishti, AH;Palek, J;Liu, SC
通讯作者：
Liu, SC
影响因子：
--
作者：
Cooke BM;Mohandas N;Coppel RL
通讯作者：
Coppel RL