6F5O

A mechanism for the activation of the influenza virus transcriptase

Summary for 6F5O

• Entry DOI: 10.2210/pdb6f5o/pdb
• EMDB information: 4190
• Descriptor: Polymerase acidic protein, RNA-directed RNA polymerase catalytic subunit, Polymerase basic protein 2, ... (5 entities in total)
• Functional Keywords: influenza virus rna dependent rna polymerase, viral protein
• Biological source: Influenza B virus (B/Memphis/13/2003); More
• Total number of polymer chains: 5
• Total formula weight: 264572.97

Authors

Serna Martin, I.,Grimes, J.M. (deposition date: 2017-12-02, release date: 2018-06-27, Last modification date: 2024-05-15)

Primary citation

Serna Martin, I.,Hengrung, N.,Renner, M.,Sharps, J.,Martinez-Alonso, M.,Masiulis, S.,Grimes, J.M.,Fodor, E.
A Mechanism for the Activation of the Influenza Virus Transcriptase.
Mol. Cell, 70:1101-1110.e4, 2018

PubMed Abstract: 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 (FluPol) bound to a Ser5-phosphorylated CTD (pS-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 FluPol are enhanced in the presence of pS-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 pS-CTD of Pol II.

PubMed: 29910112
DOI: 10.1016/j.molcel.2018.05.011

Experimental method

ELECTRON MICROSCOPY (9.8 Å)