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疟原虫感染红细胞表面的M介导的抗变性P2四聚体可导入血清脂肪酸。

M--M mediated denaturation resistant P2 tetramer on the infected erythrocyte surface of malaria parasite imports serum fatty acids.

作者信息

Das Sudipta, Manna Anwesa, Majumdar Oindrila, Dhara Lena

机构信息

Division of infectious Disease and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C Mullick Road, Jadavpur, Kolkata 700032, India.

出版信息

iScience. 2024 Apr 16;27(5):109760. doi: 10.1016/j.isci.2024.109760. eCollection 2024 May 17.

Abstract

In , DNA replication, and asynchronous nuclear divisions precede cytokinesis during intraerythrocytic schizogony. Regulation of nuclear division through the import of serum components was largely unknown. At the trophozoite stage, ribosomal protein P2 (PfP2) is exported to the infected erythrocyte (IE) cytosol and the surface as a denaturation-resistant tetramer. The inaccessibility of the IE surface exposed PfP2 to its bona fide ligand led to the arrest of nuclear division. Here, we show that at the onset of schizogony, denaturation-resistant PfP2 tetramer on the IE surface imports fatty acids (FAs). Blockage of import reversibly arrested parasite schizogony. In Met--Met mediated denaturation resistant PfP2 tetramer, the Cys-Cys redox switch regulates the binding and release of FAs based on oxidized/reduced state of disulfide linkages. This mechanistic insight of FAs import through PfP2 tetramer reveals a unique regulation of nuclear division at the onset of schizogony.

摘要

在红细胞内裂体增殖过程中,DNA复制和异步核分裂先于胞质分裂。通过血清成分的导入来调节核分裂在很大程度上尚不清楚。在滋养体阶段,核糖体蛋白P2(PfP2)作为一种抗变性的四聚体被输出到被感染红细胞(IE)的细胞质和表面。IE表面暴露的PfP2无法接触到其真正的配体导致核分裂停滞。在这里,我们表明在裂体增殖开始时,IE表面抗变性的PfP2四聚体导入脂肪酸(FAs)。导入的阻断可逆地阻止了寄生虫的裂体增殖。在甲硫氨酸 - 甲硫氨酸介导的抗变性PfP2四聚体中,半胱氨酸 - 半胱氨酸氧化还原开关根据二硫键的氧化/还原状态调节FAs的结合和释放。这种通过PfP2四聚体导入FAs的机制性见解揭示了裂体增殖开始时核分裂的独特调节方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58a1/11079477/ef08fff7f17b/fx1.jpg

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