Department of Cell & Developmental Biology, Biocenter University of Würzburg, Würzburg 97074, Germany.
Quantitative Proteomics, Institute of Molecular Biology (IMB), Mainz 55128, Germany.
Nucleic Acids Res. 2018 Apr 6;46(6):2820-2833. doi: 10.1093/nar/gky028.
During its life cycle, Trypanosoma brucei shuttles between a mammalian host and the tsetse fly vector. In the mammalian host, immune evasion of T. brucei bloodstream form (BSF) cells relies on antigenic variation, which includes monoallelic expression and periodic switching of variant surface glycoprotein (VSG) genes. The active VSG is transcribed from only 1 of the 15 subtelomeric expression sites (ESs). During differentiation from BSF to the insect-resident procyclic form (PCF), the active ES is transcriptionally silenced. We used mass spectrometry-based interactomics to determine the composition of telomere protein complexes in T. brucei BSF and PCF stages to learn more about the structure and functions of telomeres in trypanosomes. Our data suggest a different telomere complex composition in the two forms of the parasite. One of the novel telomere-associated proteins, TelAP1, forms a complex with telomeric proteins TbTRF, TbRAP1 and TbTIF2 and influences ES silencing kinetics during developmental differentiation.
在生命周期中,布氏锥虫在哺乳动物宿主和采采蝇媒介之间穿梭。在哺乳动物宿主中,布氏锥虫血流形式(BSF)细胞的免疫逃避依赖于抗原变异,包括单等位基因表达和变异表面糖蛋白(VSG)基因的周期性切换。活性 VSG 仅从 15 个端粒表达位点(ES)中的 1 个转录。在从 BSF 分化为昆虫驻留的前鞭毛体(PCF)过程中,活性 ES 被转录沉默。我们使用基于质谱的相互作用组学来确定布氏锥虫 BSF 和 PCF 阶段端粒蛋白复合物的组成,以更多地了解端粒在锥虫中的结构和功能。我们的数据表明寄生虫的两种形式具有不同的端粒复合物组成。一种新的端粒相关蛋白 TelAP1 与端粒蛋白 TbTRF、TbRAP1 和 TbTIF2 形成复合物,并影响发育分化过程中 ES 沉默的动力学。