Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding

Pierre Fechter, Louise Mingay, Jane Sharps, Anna Chambers, Ervin Fodor, George G Brownlee

Research output: Contribution to journalArticle (Academic Journal)peer-review

122 Citations (Scopus)

Abstract

mRNAs are capped at their 5'-end by a unique cap structure containing N7-methyl guanine. Recognition of the cap structure is of paramount importance in some of the most central processes of gene expression as well as in some viral processes, such as priming of influenza virus transcription. The recent resolution of the structure of three evolutionary unrelated cap binding proteins, the vaccinia viral protein VP39, the eukaryotic translation factor eIF4E, and the nuclear cap-binding protein CBP20 showed that the recognition of the cap structure is achieved by the same general mechanism, i.e. by "sandwiching" of the N7-methyl guanine of the cap structure between two aromatic amino acid residues. The purpose of the present study was to test whether a similar cap recognition mechanism had independently evolved for the RNA polymerase of influenza virus. Combining in vivo and in vitro methods, we characterized two crucial aromatic amino acids, Phe363 and Phe404, in the PB2 subunit of the viral RNA polymerase that are essential for cap binding. The aromaticity of these two residues is conserved in influenza A, B, and C and even in the divergent Thogoto virus PB2 subunits. Thus, our results favor a similar mechanism of cap binding by the influenza RNA polymerase as in the evolutionary unrelated VP39, eIF4E, and CBP20.

Original languageEnglish
Pages (from-to)20381-8
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number22
DOIs
Publication statusPublished - 30 May 2003

Keywords

  • Amino Acid Sequence
  • Base Sequence
  • DNA Primers
  • DNA-Directed RNA Polymerases
  • Globins
  • Influenza A virus
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • RNA Caps
  • RNA, Messenger
  • Recombination, Genetic
  • Sequence Homology, Amino Acid

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