Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains
Copyright policy )Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains
Influenza virus polymerase transcribes or replicates the segmented RNA genome (vRNA) into respectively viral mRNA or full-length copies and initiates RNA synthesis by binding the conserved 3' and 5' 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 structure with a bound complementary cRNA 5' 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 Å to bind to the endonuclease domain. FluA PB2-C alone and RNA-free FluC polymerase are similarly arranged. Biophysical and cap-dependent endonuclease assays show that in solution the polymerase explores different conformational distributions depending on which RNA is bound. The inherent flexibility of the polymerase allows it to adopt alternative conformations that are likely important during polymerase maturation into active progeny RNPs.
- French National Centre for Scientific Research France
- Sir William Dunn School of Pathology, University of Oxford United Kingdom
- European Molecular Biology Laboratory Germany
- Commissariat à l’Energie Atomique et aux Energies Alternatives France
- European Molecular Biology Laboratory, Structural and Computational Biology Unit Germany
Small Angle, Models, Molecular, Nuclear Localization Signals, MESH: Nuclear Localization Signals, MESH: Amino Acid Sequence, Crystallography, X-Ray, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Mass Spectrometry, MESH: Influenzavirus C, MESH: Structure-Activity Relationship, MESH: Models, Viral, MESH: Influenza B virus, Gammainfluenzavirus, MESH: Crystallography, Ribonucleoproteins, MESH: Lasers, RNA, Viral, H5N1 Subtype, MESH: RNA Replicase, 570, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Sequence Data, Article, Structure-Activity Relationship, Viral Proteins, MESH: RNA, Scattering, Small Angle, Humans, Protein Interaction Domains and Motifs, Amino Acid Sequence, Molecular Biology, MESH: Mass Spectrometry, MESH: Protein Interaction Domains and Motifs, MESH: Humans, MESH: Molecular Sequence Data, Influenza A Virus, H5N1 Subtype, Molecular Biology/Structural Biology [q-bio.BM], Lasers, Molecular, Cell Biology, MESH: Influenza A Virus, 540, RNA-Dependent RNA Polymerase, MESH: Viral Proteins, MESH: Ribonucleoproteins, Influenza B virus, MESH: Scattering, X-Ray
Small Angle, Models, Molecular, Nuclear Localization Signals, MESH: Nuclear Localization Signals, MESH: Amino Acid Sequence, Crystallography, X-Ray, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Mass Spectrometry, MESH: Influenzavirus C, MESH: Structure-Activity Relationship, MESH: Models, Viral, MESH: Influenza B virus, Gammainfluenzavirus, MESH: Crystallography, Ribonucleoproteins, MESH: Lasers, RNA, Viral, H5N1 Subtype, MESH: RNA Replicase, 570, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Sequence Data, Article, Structure-Activity Relationship, Viral Proteins, MESH: RNA, Scattering, Small Angle, Humans, Protein Interaction Domains and Motifs, Amino Acid Sequence, Molecular Biology, MESH: Mass Spectrometry, MESH: Protein Interaction Domains and Motifs, MESH: Humans, MESH: Molecular Sequence Data, Influenza A Virus, H5N1 Subtype, Molecular Biology/Structural Biology [q-bio.BM], Lasers, Molecular, Cell Biology, MESH: Influenza A Virus, 540, RNA-Dependent RNA Polymerase, MESH: Viral Proteins, MESH: Ribonucleoproteins, Influenza B virus, MESH: Scattering, X-Ray
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