Molecular Cell ( IF 16.0 ) Pub Date : 2017-12-28 , DOI: 10.1016/j.molcel.2017.11.034 Thomas Kruse , Nadine Biedenkopf , Emil Peter Thrane Hertz , Erik Dietzel , Gertrud Stalmann , Blanca López-Méndez , Norman E. Davey , Jakob Nilsson , Stephan Becker
Transcription of the Ebola virus genome depends on the viral transcription factor VP30 in its unphosphorylated form, but the underlying molecular mechanism of VP30 dephosphorylation is unknown. Here we show that the Ebola virus nucleoprotein (NP) recruits the host PP2A-B56 protein phosphatase through a B56-binding LxxIxE motif and that this motif is essential for VP30 dephosphorylation and viral transcription. The LxxIxE motif and the binding site of VP30 in NP are in close proximity, and both binding sites are required for the dephosphorylation of VP30. We generate a specific inhibitor of PP2A-B56 and show that it suppresses Ebola virus transcription and infection. This work dissects the molecular mechanism of VP30 dephosphorylation by PP2A-B56, and it pinpoints this phosphatase as a potential target for therapeutic intervention.
中文翻译:
埃博拉病毒核蛋白募集宿主PP2A-B56磷酸酶以激活VP30的转录支持活性
埃博拉病毒基因组的转录取决于未磷酸化形式的病毒转录因子VP30,但VP30去磷酸化的潜在分子机制尚不清楚。在这里,我们显示埃博拉病毒核蛋白(NP)通过结合B56的LxxIxE基序募集了宿主PP2A-B56蛋白磷酸酶,并且该基序对于VP30的去磷酸化和病毒转录是必不可少的。LxxIxE基序与NP中VP30的结合位点非常接近,并且两个结合位点都是VP30的去磷酸化所必需的。我们产生了PP2A-B56的特异性抑制剂,并显示它抑制了埃博拉病毒的转录和感染。这项工作剖析了PP2A-B56 VP30去磷酸化的分子机制,并指出了该磷酸酶是治疗干预的潜在靶标。