A Mechanism for the Activation of the Influenza Virus Transcriptase

作者：Martin Itziar Serna; Hengrung Narin; Renner Max; Sharps Jane; Martinez Alonso Monica; Masiulis Simonas; Grimes Jonathan M^*; Fodor Ervin^*

来源：Molecular Cell, 2018, 70(6): 1101-+.

DOI：10.1016/j.molcel.2018.05.011

Influenza virus RNA polymerase (FluPol), a heterotrimer composed of PB1, PB2, and PA subunits (P3 in influenza C), performs both transcription and replication of the viral RNA genome. For transcription, FluPol interacts with the C-terminal domain (CTD) of RNA polymerase II (Pol II), which enables FluPol to snatch capped RNA primers from nascent host RNAs. Here, we describe the co-crystal structure of influenza C virus polymerase (FluPolC) bound to a Ser5-phosphorylated CTD (pS5-CTD) peptide. The position of the CTD-binding site at the interface of PB1, P3, and the flexible PB2 C-terminal domains suggests that CTD binding stabilizes the transcription- competent conformation of FluPol. In agreement, both cap snatching and capped primer-dependent transcription initiation by FluPolC are enhanced in the presence of pS5-CTD. Mutations of amino acids in the CTD-binding site reduce viral mRNA synthesis. We propose a model for the activation of the influenza virus transcriptase through its association with pS5-CTD of Pol II.

• 出版日期2018-6-21
• 单位西北大学