当前位置: X-MOL 学术EMBO J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Non-canonical proline-tyrosine interactions with multiple host proteins regulate Ebola virus infection
The EMBO Journal ( IF 11.4 ) Pub Date : 2021-08-02 , DOI: 10.15252/embj.2020105658
Jyoti Batra 1, 2, 3 , Hiroyuki Mori 4 , Gabriel I Small 5, 6 , Manu Anantpadma 4 , Olena Shtanko 7 , Nawneet Mishra 5 , Mengru Zhang 8 , Dandan Liu 5 , Caroline G Williams 9 , Nadine Biedenkopf 10 , Stephan Becker 10 , Michael L Gross 8 , Daisy W Leung 5, 6 , Robert A Davey 4 , Gaya K Amarasinghe 5 , Nevan J Krogan 1, 2, 3 , Christopher F Basler 9
Affiliation  

The Ebola virus VP30 protein interacts with the viral nucleoprotein and with host protein RBBP6 via PPxPxY motifs that adopt non-canonical orientations, as compared to other proline-rich motifs. An affinity tag-purification mass spectrometry approach identified additional PPxPxY-containing host proteins hnRNP L, hnRNPUL1, and PEG10, as VP30 interactors. hnRNP L and PEG10, like RBBP6, inhibit viral RNA synthesis and EBOV infection, whereas hnRNPUL1 enhances. RBBP6 and hnRNP L modulate VP30 phosphorylation, increase viral transcription, and exert additive effects on viral RNA synthesis. PEG10 has more modest inhibitory effects on EBOV replication. hnRNPUL1 positively affects viral RNA synthesis but in a VP30-independent manner. Binding studies demonstrate variable capacity of the PPxPxY motifs from these proteins to bind VP30, define PxPPPPxY as an optimal binding motif, and identify the fifth proline and the tyrosine as most critical for interaction. Competition binding and hydrogen-deuterium exchange mass spectrometry studies demonstrate that each protein binds a similar interface on VP30. VP30 therefore presents a novel proline recognition domain that is targeted by multiple host proteins to modulate viral transcription.

中文翻译:

非经典脯氨酸-酪氨酸与多种宿主蛋白​​的相互作用调节埃博拉病毒感染

与其他富含脯氨酸的基序相比,埃博拉病毒 VP30 蛋白通过采用非规范方向的 PPxPxY 基序与病毒核蛋白和宿主蛋白 RBBP6 相互作用。亲和标签纯化质谱方法确定了额外的含有 PPxPxY 的宿主蛋白 hnRNP L、hnRNPUL1 和 PEG10,作为 VP30 相互作用物。hnRNP L 和 PEG10 与 RBBP6 一样,抑制病毒 RNA 合成和 EBOV 感染,而 hnRNPUL1 增强。RBBP6 和 hnRNP L 调节 VP30 磷酸化,增加病毒转录,并对病毒 RNA 合成产生累加效应。PEG10 对 EBOV 复制具有更温和的抑制作用。hnRNPUL1 对病毒 RNA 合成有积极影响,但不依赖于 VP30。结合研究表明这些蛋白质的 PPxPxY 基序结合 VP30 的能力不同,将 PxPPPPxY 定义为最佳结合基序,并确定第五个脯氨酸和酪氨酸对相互作用最关键。竞争结合和氢氘交换质谱研究表明,每种蛋白质与 VP30 上的相似界面结合。因此,VP30 提供了一个新的脯氨酸识别域,它被多种宿主蛋白​​靶向以调节病毒转录。
更新日期:2021-09-15
down
wechat
bug