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战胜锥虫类寄生虫“三巨头”:导致被忽视热带病的原生动物寄生虫蛋白质组学

Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases.

作者信息

Parthasarathy Anutthaman, Kalesh Karunakaran

机构信息

Rochester Institute of Technology , Thomas H. Gosnell School of Life Sciences , 85 Lomb Memorial Dr , Rochester , NY 14623 , USA.

Department of Chemistry , Durham University , Lower Mount Joy, South Road , Durham DH1 3LE , UK . Email:

出版信息

RSC Med Chem. 2020 May 22;11(6):625-645. doi: 10.1039/d0md00122h. eCollection 2020 Jun 1.

DOI:10.1039/d0md00122h
PMID:33479664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7549140/
Abstract

Mass spectrometry-based proteomics enables accurate measurement of the modulations of proteins on a large scale upon perturbation and facilitates the understanding of the functional roles of proteins in biological systems. It is a particularly relevant methodology for studying spp., and , as the gene expression in these parasites is primarily regulated by posttranscriptional mechanisms. Large-scale proteomics studies have revealed a plethora of information regarding modulated proteins and their molecular interactions during various life processes of the protozoans, including stress adaptation, life cycle changes and interactions with the host. Important molecular processes within the parasite that regulate the activity and subcellular localisation of its proteins, including several co- and post-translational modifications, are also accurately captured by modern proteomics mass spectrometry techniques. Finally, in combination with synthetic chemistry, proteomic techniques facilitate unbiased profiling of targets and off-targets of pharmacologically active compounds in the parasites. This provides important data sets for their mechanism of action studies, thereby aiding drug development programmes.

摘要

基于质谱的蛋白质组学能够在受到扰动时大规模地准确测量蛋白质的调节情况,并有助于理解蛋白质在生物系统中的功能作用。对于研究某些物种以及其他相关物种而言,这是一种特别适用的方法,因为这些寄生虫中的基因表达主要受转录后机制调控。大规模蛋白质组学研究已经揭示了大量有关原生动物在各种生命过程中调节蛋白质及其分子相互作用的信息,包括应激适应、生命周期变化以及与宿主的相互作用。寄生虫体内调节其蛋白质活性和亚细胞定位的重要分子过程,包括几种共翻译和翻译后修饰,也能被现代蛋白质组学质谱技术准确捕获。最后,结合合成化学,蛋白质组学技术有助于对寄生虫中药理活性化合物的靶标和脱靶进行无偏分析。这为其作用机制研究提供了重要数据集,从而有助于药物开发计划。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/eddc83f34b46/d0md00122h-p2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/8b84c901216f/d0md00122h-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/9f331773786b/d0md00122h-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/7d08ed72aa33/d0md00122h-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/c1e8a1de15bd/d0md00122h-p1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/eddc83f34b46/d0md00122h-p2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/8b84c901216f/d0md00122h-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/24eed2b8ac01/d0md00122h-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/9f331773786b/d0md00122h-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/7d08ed72aa33/d0md00122h-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94c/7549140/c1e8a1de15bd/d0md00122h-p1.jpg
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