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Activity-Based Phosphatidylinositol Kinase Probes Detect Changes to Protein–Protein Interactions During Hepatitis C Virus Replication
ACS Infectious Diseases ( IF 5.3 ) Pub Date : 2018-03-06 00:00:00 , DOI: 10.1021/acsinfecdis.8b00047
Geneviève F. Desrochers 1 , Christina Cornacchia 1 , Craig S. McKay 1 , John Paul Pezacki 1, 2
Affiliation  

Protein–protein interactions are integral to host–virus interactions and can contribute significantly to enzyme regulation by changing the localization of both host and viral enzymes within the cell, inducing conformational change relevant to enzyme activity or recruiting other additional proteins to form functional complexes. Identifying the interactors of active enzymes using an activity-based protein profiling probe has allowed us to characterize both normal enzyme activation mechanisms and the manner by which these mechanisms are hijacked and altered by the hepatitis C virus (HCV). Here, we report use of a novel activity-based probe, PIKBPyne, which labels phosphatidylinositol kinases (PIKs) in an activity-based manner, to investigate HCV-dependent changes in protein–protein interactions for PI4KB. Herein, we report the synthesis of new variations on PIKBPyne, compare their ability to label the interacting partners of PI4KB, and demonstrate the utility of our approach in characterizing virus-mediated changes to host function.

中文翻译:

基于活动的磷脂酰肌醇激酶探针检测丙型肝炎病毒复制过程中蛋白质与蛋白质相互作用的变化

蛋白质与蛋白质的相互作用是宿主与病毒相互作用不可或缺的,并且可以通过改变细胞内宿主和病毒酶的定位,诱导与酶活性有关的构象变化或募集其他蛋白质来形成功能复合物,从而对酶的调节做出重要贡献。使用基于活性的蛋白谱分析探针鉴定活性酶的相互作用因子,使我们能够表征正常的酶激活机制以及丙型肝炎病毒(HCV)劫持和改变这些机制的方式。在这里,我们报道了一种新颖的基于活性的探针PIKBPyne的使用,该探针以基于活性的方式标记了磷脂酰肌醇激酶(PIK),以研究HCV依赖的PI4KB蛋白相互作用中的变化。在此处,
更新日期:2018-03-06
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