Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites
Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites
复制标题
红细胞结合蛋白的连续作用使得疟疾寄生虫能够分阶段入侵
DOI：
10.1101/2022.08.09.503398
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Hart M
中科院分区：
文献类型：
--
作者：
Hart M
疟原虫裂殖子侵入红细胞是其在宿主体内持续生存的关键。两个主要的蛋白质家族，Duffy结合样蛋白（DBPs/EBA）和网织红细胞结合样蛋白（RBL/RH）已被广泛研究。假设恶性疟原虫和恶性疟原虫在进入宿主细胞之前具有重叠的但关键的作用。人畜共患疟疾寄生虫诺氏疟原虫具有较大的侵入性裂殖子，并且含有比诺氏疟原虫更小、更少冗余的DBP和RBL库。恶性疟原虫。一种DBP（DBPα）和一种RBL，正常细胞结合蛋白Xa（NBPXa）是人红细胞侵袭所必需的。利用P.通过对CRISPR-Cas9基因组的反复编辑，我们确定了关键入侵里程碑的精确顺序，并展示了每个家族的独特作用。这些不同的作用支持分阶段侵入的机制，并且可以与侵入抑制抗体协同靶向。
Invasion of red blood cells (RBCs) byPlasmodiummerozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively inP. falciparumand are hypothesized to have overlapping, but critical roles just prior to host cell entry. The zoonotic malaria parasite,P. knowlesi, has larger invasive merozoites and contains a smaller, less redundant, DBP and RBL repertoire thanP. falciparum. One DBP (DBPα) and one RBL, normocyte binding protein Xa (NBPXa) are essential for invasion of human RBCs. Taking advantage of the unique biological features ofP. knowlesiand iterative CRISPR-Cas9 genome editing, we determine the precise order of key invasion milestones and demonstrate distinct roles for each family. These distinct roles support a mechanism for phased commitment to invasion and can be targeted synergistically with invasion inhibitory antibodies.
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