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.
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DOI：
10.1038/s41467-023-40357-z
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发表时间：
2023-08-01
影响因子：
16.6
通讯作者：
Moon, Robert W.
中科院分区：
文献类型：
--
作者：
Hart, Melissa N.;Mohring, Franziska;DonVito, Sophia M.;Thomas, James A.;Mueller-Sienerth, Nicole;Wright, Gavin J.;Knuepfer, Ellen;Saibil, Helen R.;Moon, Robert W.
疟原虫分裂子入侵红细胞（rbc）对其在宿主体内的持续存活至关重要。两个主要的蛋白家族，Duffy结合样蛋白（DBPs/EBAs）和网状细胞结合样蛋白（RBLs/RHs）已经在恶性疟原虫中进行了广泛的研究，并且假设它们在宿主细胞进入之前具有重叠但关键的作用。与恶性疟原虫相比，人畜共患疟疾寄生虫诺氏疟原虫具有更大的侵入性分殖子，并包含更小、更少冗余的DBP和RBL库。一个DBP （DBPα）和一个RBL，正常细胞结合蛋白Xa （NBPXa）是入侵人红细胞所必需的。利用诺氏疟原虫独特的生物学特征和迭代CRISPR-Cas9基因组编辑，我们确定了关键入侵里程碑的精确顺序，并证明了每个家族的不同作用。这些不同的作用支持了一种分阶段进行侵袭的机制，并且可以与侵袭抑制抗体协同靶向。疟疾寄生虫侵入红细胞增殖，但可视化这一快速过程是具有挑战性的。在这里，作者使用诺氏疟原虫的实时成像和基因组编辑来解剖入侵并确定两种重要寄生虫蛋白的作用。
Invasion of red blood cells (RBCs) by Plasmodium merozoites 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 in P. falciparum and 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 than P. 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 of P. knowlesi and 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. Malaria parasites invade erythrocytes to proliferate, but visualizing this rapid process is challenging. Here the authors use live imaging and genome-editing of P. knowlesi to dissect invasion and establish the roles of two vital parasite proteins.
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鉴定与PFRH4红细胞结合域同源的疟原虫网状细胞结合蛋白1的网状细胞特异性结合结构域。
影响因子：
4.6
作者：
Han JH;Lee SK;Wang B;Muh F;Nyunt MH;Na S;Ha KS;Hong SH;Park WS;Sattabongkot J;Tsuboi T;Han ET
通讯作者：
Han ET
影响因子：
13.6
作者：
Balestra AC;Koussis K;Klages N;Howell SA;Flynn HR;Bantscheff M;Pasquarello C;Perrin AJ;Brusini L;Arboit P;Sanz O;Castaño LP;Withers-Martinez C;Hainard A;Ghidelli-Disse S;Snijders AP;Baker DA;Blackman MJ;Brochet M
通讯作者：
Brochet M
影响因子：
6.7
作者：
Baker RP;Wijetilaka R;Urban S
通讯作者：
Urban S
DOI：
10.1073/pnas.1522469113
发表时间：
2016-06-28
影响因子：
11.1
作者：
Moon, Robert W.;Sharaf, Hazem;Holder, Anthony A.
通讯作者：
Holder, Anthony A.
影响因子：
3.4
作者：
Gunalan, Karthigayan;Gao, Xiaohong;Preiser, Peter R.
通讯作者：
Preiser, Peter R.