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Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit.

Xie L, Wartchow C, Shia S, Uehara K, Steffek M, Warne R, Sutton J, Muiru GT, Leonard VH, Bussiere DE, Ma X
J Biol Chem 291 363-70 (2016)
Related entries: 5ef9, 5efc

Cited: 11 times
EuropePMC logo PMID: 26559973

Abstract

Influenza virus polymerase catalyzes the transcription of viral mRNAs by a process known as "cap-snatching," where the 5'-cap of cellular pre-mRNA is recognized by the PB2 subunit and cleaved 10-13 nucleotides downstream of the cap by the endonuclease PA subunit. Although this mechanism is common to both influenza A (FluA) and influenza B (FluB) viruses, FluB PB2 recognizes a wider range of cap structures including m(7)GpppGm-, m(7)GpppG-, and GpppG-RNA, whereas FluA PB2 utilizes methylated G-capped RNA specifically. Biophysical studies with isolated PB2 cap-binding domain (PB2(cap)) confirm that FluB PB2 has expanded mRNA cap recognition capability, although the affinities toward m(7)GTP are significantly reduced when compared with FluA PB2. The x-ray co-structures of the FluB PB2(cap) with bound cap analogs m(7)GTP and GTP reveal an inverted GTP binding mode that is distinct from the cognate m(7)GTP binding mode shared between FluA and FluB PB2. These results delineate the commonalities and differences in the cap-binding site between FluA and FluB PB2 and will aid structure-guided drug design efforts to identify dual inhibitors of both FluA and FluB PB2.

Reviews - 5efa mentioned but not cited (1)

  1. The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design. Stevaert A, Naesens L. Med Res Rev 36 1127-1173 (2016)

Articles - 5efa mentioned but not cited (2)

  1. Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit. Xie L, Wartchow C, Shia S, Uehara K, Steffek M, Warne R, Sutton J, Muiru GT, Leonard VH, Bussiere DE, Ma X. J Biol Chem 291 363-370 (2016)
  2. Identification of Novel Influenza Polymerase PB2 Inhibitors Using a Cascade Docking Virtual Screening Approach. Zhao L, Che J, Zhang Q, Li Y, Guo X, Chen L, Li H, Cao R, Li X. Molecules 25 E5291 (2020)


Reviews citing this publication (4)

  1. Antiviral therapies on the horizon for influenza. Naesens L, Stevaert A, Vanderlinden E. Curr Opin Pharmacol 30 106-115 (2016)
  2. Structure and Function of Influenza Polymerase. Wandzik JM, Kouba T, Cusack S. Cold Spring Harb Perspect Med 11 a038372 (2021)
  3. Biochemical principles and inhibitors to interfere with viral capping pathways. Decroly E, Canard B. Curr Opin Virol 24 87-96 (2017)
  4. A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell. Herbert KM, Nag A. Viruses 8 E154 (2016)

Articles citing this publication (4)

  1. Fragment-Based Identification of Influenza Endonuclease Inhibitors. Credille CV, Chen Y, Cohen SM. J Med Chem 59 6444-6454 (2016)
  2. Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors. Pflug A, Gaudon S, Resa-Infante P, Lethier M, Reich S, Schulze WM, Cusack S. Nucleic Acids Res 46 956-971 (2018)
  3. Molecular characterization of emaraviruses associated with Pigeonpea sterility mosaic disease. Kumar S, Subbarao BL, Hallan V. Sci Rep 7 11831 (2017)
  4. A Parallel Phenotypic Versus Target-Based Screening Strategy for RNA-Dependent RNA Polymerase Inhibitors of the Influenza A Virus. Zhao X, Wang Y, Cui Q, Li P, Wang L, Chen Z, Rong L, Du R. Viruses 11 E826 (2019)


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