一种与恶性疟原虫感染的红细胞上的 VAR2CSA 共定位的不变蛋白与硫酸软骨素 A 结合。
An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A.
机构信息
Center for Infectious Disease Research, Seattle, Washington, USA.
University of Washington, Department of Pathobiology, Seattle, Washington, USA.
出版信息
J Infect Dis. 2022 Jun 1;225(11):2011-2022. doi: 10.1093/infdis/jiab550.
BACKGROUND
Plasmodium falciparum-infected red blood cells (iRBCs) bind and sequester in deep vascular beds, causing malaria-related disease and death. In pregnant women, VAR2CSA binds to chondroitin sulfate A (CSA) and mediates placental sequestration, making it the major placental malaria (PM) vaccine target.
METHODS
In this study, we characterize an invariant protein associated with PM called P falciparum chondroitin sulfate A ligand (PfCSA-L).
RESULTS
Recombinant PfCSA-L binds both placental CSA and VAR2CSA with nanomolar affinity, and it is coexpressed on the iRBC surface with VAR2CSA. Unlike VAR2CSA, which is anchored by a transmembrane domain, PfCSA-L is peripherally associated with the outer surface of knobs through high-affinity protein-protein interactions with VAR2CSA. This suggests that iRBC sequestration involves complexes of invariant and variant surface proteins, allowing parasites to maintain both diversity and function at the iRBC surface.
CONCLUSIONS
The PfCSA-L is a promising target for intervention because it is well conserved, exposed on infected cells, and expressed and localized with VAR2CSA.
背景
恶性疟原虫感染的红细胞（iRBC）与硫酸软骨素 A（CSA）结合并定位于深血管床，导致疟疾相关疾病和死亡。在孕妇中，VAR2CSA 与 CSA 结合并介导胎盘定位于，使其成为主要的胎盘疟疾（PM）疫苗靶点。
方法
在这项研究中，我们描述了一种与 PM 相关的称为 Pf 寄生虫 CSA 配体（PfCSA-L）的不变蛋白。
结果
重组 PfCSA-L 以纳摩尔亲和力结合胎盘 CSA 和 VAR2CSA，并且与 VAR2CSA 共表达在 iRBC 表面。与由跨膜结构域锚定的 VAR2CSA 不同，PfCSA-L 通过与 VAR2CSA 的高亲和力蛋白-蛋白相互作用与 knob 的外表面周边相关。这表明 iRBC 定位于涉及不变和可变表面蛋白的复合物，允许寄生虫在 iRBC 表面保持多样性和功能。
结论
PfCSA-L 是一种有前途的干预靶点，因为它具有良好的保守性，在感染细胞上表达并定位于 VAR2CSA。
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