Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains

Abstract

Influenza virus polymerase transcribes or repli- cates the segmented RNA genome (vRNA) into respectively viral mRNA or full-length copies and ini- tiates RNA synthesis by binding the conserved 30 and 50 vRNA ends (the promoter). In recent structures of promoter-bound polymerase, the cap-binding and endonuclease domains are configured for cap snatching, which generates capped transcription primers. Here, we present a FluB polymerase struc- ture with a bound complementary cRNA 50 end that exhibits a major rearrangement of the subdomains within the C-terminal two-thirds of PB2 (PB2-C). Notably, the PB2 nuclear localization signal (NLS)- containing domain translocates 90 A˚ to bind to the endonuclease domain. FluA PB2-C alone and RNA-free FluC polymerase are similarly arranged. Biophysical and cap-dependent endonuclease as- says show that in solution the polymerase explores different conformational distributions depending on which RNA is bound. The inherent flexibility of the po- lymerase allows it to adopt alternative conformations that are likely important during polymerase matura- tion into active progeny RNPs.

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Cite

BibTeX RIS

BibTeX

@article{thierry2026influenza,
  title = {{Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains}},
  author = {Eric Thierry and Delphine Guilligay and Jan Kosinski and Thomas Bock and Stephanie Gaudon and Adam Round and Alexander Pflug and Narin Hengrung and Kamel El Omari and Florence Baudin and Darren J Hart and Martin Beck and Stephen Cusack},
  journal = {Molecular Cell},
  year = {2026},
  month = oct,
  doi = {10.1016/j.molcel.2015.11.016},
  url = {https://hal.science/hal-05797560v1},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains
AU  - Eric Thierry
AU  - Delphine Guilligay
AU  - Jan Kosinski
AU  - Thomas Bock
AU  - Stephanie Gaudon
AU  - Adam Round
AU  - Alexander Pflug
AU  - Narin Hengrung
AU  - Kamel El Omari
AU  - Florence Baudin
AU  - Darren J Hart
AU  - Martin Beck
AU  - Stephen Cusack
PY  - 2026
DA  - 2026/10/13
JO  - Molecular Cell
DO  - 10.1016/j.molcel.2015.11.016
UR  - https://hal.science/hal-05797560v1
AB  - Influenza virus polymerase transcribes or repli- cates the segmented RNA genome (vRNA) into respectively viral mRNA or full-length copies and ini- tiates RNA synthesis by binding the conserved 30 and 50 vRNA ends (the promoter). In recent structures of promoter-bound polymerase, the cap-binding and endonuclease domains are configured for cap snatching, which generates capped transcription primers. Here, we present a FluB polymerase struc- ture with a bound complementary cRNA 50 end that exhibits a major rearrangement of the subdomains within the C-terminal two-thirds of PB2 (PB2-C). Notably, the PB2 nuclear localization signal (NLS)- containing domain translocates 90 A˚ to bind to the endonuclease domain. FluA PB2-C alone and RNA-free FluC polymerase are similarly arranged. Biophysical and cap-dependent endonuclease as- says show that in solution the polymerase explores different conformational distributions depending on which RNA is bound. The inherent flexibility of the po- lymerase allows it to adopt alternative conformations that are likely important during polymerase matura- tion into active progeny RNPs.
SN  - 1097-2765
SN  - 1097-4164
ER  -

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