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Co-opting ATP-generating glycolytic enzyme PGK1 phosphoglycerate kinase facilitates the assembly of viral replicase complexes
PLoS Pathogens ( IF 5.5 ) Pub Date : 2017-10-23 , DOI: 10.1371/journal.ppat.1006689
K Reddisiva Prasanth 1 , Chingkai Chuang 1 , Peter D Nagy 1
Affiliation  

The intricate interactions between viruses and hosts include exploitation of host cells for viral replication by using many cellular resources, metabolites and energy. Tomato bushy stunt virus (TBSV), similar to other (+)RNA viruses, induces major changes in infected cells that lead to the formation of large replication compartments consisting of aggregated peroxisomal and ER membranes. Yet, it is not known how TBSV obtains the energy to fuel these energy-consuming processes. In the current work, the authors discovered that TBSV co-opts the glycolytic ATP-generating Pgk1 phosphoglycerate kinase to facilitate the assembly of new viral replicase complexes. The recruitment of Pgk1 into the viral replication compartment is through direct interaction with the viral replication proteins. Altogether, we provide evidence that the ATP generated locally within the replication compartment by the co-opted Pgk1 is used to fuel the ATP-requirement of the co-opted heat shock protein 70 (Hsp70) chaperone, which is essential for the assembly of new viral replicase complexes and the activation of functional viral RNA-dependent RNA polymerase. The advantage of direct recruitment of Pgk1 into the virus replication compartment could be that the virus replicase assembly does not need to intensively compete with cellular processes for access to ATP. In addition, local production of ATP within the replication compartment could greatly facilitate the efficiency of Hsp70-driven replicase assembly by providing high ATP concentration within the replication compartment.



中文翻译:


选择产生 ATP 的糖酵解酶 PGK1 磷酸甘油酸激酶促进病毒复制酶复合物的组装



病毒和宿主之间复杂的相互作用包括通过使用许多细胞资源、代谢物和能量来利用宿主细胞进行病毒复制。番茄浓密矮化病毒 (TBSV) 与其他 (+)RNA 病毒类似,可诱导受感染细胞发生重大变化,从而形成由聚集的过氧化物酶体和 ER 膜组成的大型复制区室。然而,尚不清楚 TBSV 如何获得能量来为这些耗能过程提供燃料。在目前的工作中,作者发现 TBSV 与糖酵解 ATP 生成 Pgk1 磷酸甘油酸激酶共同作用,以促进新病毒复制酶复合物的组装。 Pgk1 通过与病毒复制蛋白的直接相互作用招募到病毒复制区室中。总而言之,我们提供的证据表明,由增选的 Pgk1 在复制室内局部生成的 ATP 用于为增选的热休克蛋白 70 (Hsp70) 伴侣的 ATP 需求提供燃料,这对于新的组装过程至关重要。病毒复制酶复合物和功能性病毒RNA依赖性RNA聚合酶的激活。将 Pgk1 直接招募到病毒复制区室的优点可能是病毒复制酶组装不需要与细胞过程激烈竞争获取 ATP。此外,复制室内的 ATP 本地生产可以通过在复制室内提供高 ATP 浓度,极大地促进 Hsp70 驱动的复制酶组装的效率。

更新日期:2017-10-24
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