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蛋白质组学分析确定了原生动物寄生虫中端粒酶的相互作用组。

Proteomic analysis defines the interactome of telomerase in the protozoan parasite, .

作者信息

Davis Justin A, Reyes Andres V, Saha Arpita, Wolfgeher Donald J, Xu Shou-Ling, Truman Andrew W, Li Bibo, Chakrabarti Kausik

机构信息

Department of Biological Sciences, University of North Carolina, Charlotte, NC, United States.

Department of Plant Biology and Carnegie Mass Spectrometry Facility, Carnegie Institution for Science, Stanford, CA, United States.

出版信息

Front Cell Dev Biol. 2023 Mar 16;11:1110423. doi: 10.3389/fcell.2023.1110423. eCollection 2023.

Abstract

Telomerase is a ribonucleoprotein enzyme responsible for maintaining the telomeric end of the chromosome. The telomerase enzyme requires two main components to function: the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR), which provides the template for telomeric DNA synthesis. TR is a long non-coding RNA, which forms the basis of a large structural scaffold upon which many accessory proteins can bind and form the complete telomerase holoenzyme. These accessory protein interactions are required for telomerase activity and regulation inside cells. The interacting partners of TERT have been well studied in yeast, human, and models, but not in parasitic protozoa, including clinically relevant human parasites. Here, using the protozoan parasite, () as a model, we have identified the interactome of TERT (TERT) using a mass spectrometry-based approach. We identified previously known and unknown interacting factors of TERT, highlighting unique features of telomerase biology. These unique interactions with TERT, suggest mechanistic differences in telomere maintenance between and other eukaryotes.

摘要

端粒酶是一种核糖核蛋白酶,负责维持染色体的端粒末端。端粒酶发挥功能需要两个主要成分:端粒酶逆转录酶(TERT)和端粒酶RNA(TR),后者为端粒DNA合成提供模板。TR是一种长链非编码RNA,它构成了一个大型结构支架的基础,许多辅助蛋白可以结合在该支架上并形成完整的端粒酶全酶。这些辅助蛋白相互作用对于细胞内端粒酶的活性和调控是必需的。TERT的相互作用伙伴在酵母、人类和模型中已有深入研究,但在寄生原生动物中,包括与临床相关的人类寄生虫中尚未得到研究。在此,我们以原生动物寄生虫利什曼原虫(Leishmania)为模型,采用基于质谱的方法鉴定了利什曼原虫TERT(LmTERT)的相互作用组。我们鉴定出了LmTERT先前已知和未知的相互作用因子,突出了利什曼原虫端粒酶生物学的独特特征。这些与LmTERT的独特相互作用表明,利什曼原虫与其他真核生物在端粒维持机制上存在差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d0/10061497/3d13bfdec199/fcell-11-1110423-g001.jpg

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