Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA
Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA
复制标题
DOI：
10.1101/2021.07.02.450898
复制
发表时间：
2022-02-22
影响因子：
5.7
通讯作者：
Merrick，Catherine J.
中科院分区：
文献类型：
--
作者：
Edwards-Smallbone，James;Jensen，Anders L.;Merrick，Catherine J.
在早期发散的原生动物寄生虫疟原虫中，很少有端粒结合蛋白被鉴定出来，其中有几个是唯一的。与大多数真核生物一样，疟原虫端粒含有富含鸟嘌呤的重复序列，可以形成G-四链结构。在模型系统中，四链结合药物可以破坏端粒的维持，一些四链结合药物是有效的抗疟原虫药物。因此，端粒相互作用蛋白和四链相互作用蛋白可能为抗疟疾治疗提供新的靶点。在这里，我们报告P。恶性疟原虫GBP2就是这样一种蛋白质。在体外，PfGBP2以四链形式与富含G的端粒重复序列特异性结合，也可以与富含G的RNA结合。在体内，PfGBP2与已知的端粒蛋白HP1部分共存，但也存在于细胞质中，可能是因为它与RNA的亲和力。PfGBP2在疟原虫中是一种多功能的DNA/RNA结合因子。
In the early-diverging protozoan parasitePlasmodium, few telomere-binding proteins have been identified and several are unique.Plasmodiumtelomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report thatP. falciparumGBP2 is such a protein. It was identifiedvia‘Proteomics of Isolated Chromatin fragments’, applied here for the first time inPlasmodium.In vitro,PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA.In vivo,PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins.PfGBP2 is evidently a multifunctional DNA/RNA-binding factor inPlasmodium.