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PXD030816-2

PXD030816 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe ubiquitin landscape of the Influenza A Virus polymerase
DescriptionDuring influenza A virus (IAV) infections, viral proteins are targeted by cellular E3 ligases for modification with ubiquitin. Here, we decipher and functionally explore the ubiquitin landscape of the IAV polymerase during infection of human alveolar epithelial cells by applying mass spectrometry analysis of immuno-purified K-ε-GG- (di-glycyl)-remnant-bearing peptides. We identified 59 modified lysines across all three subunits of the viral polymerase of which 17 distinctively affected mRNA transcription, vRNA replication and the generation of recombinant viruses via non-proteolytic mechanisms. Moreover, our results demonstrate that the ubiquitinated residue K578 in the PB1 thumb domain is crucial for the dynamic structural transitions of the viral polymerase that are required for vRNA replication. Mutations K578A and K578R impeded the steps of cRNA stabilization and vRNA transcription, respectively, and affected NP binding as well as polymerase dimerization. Collectively, our results indicate that ubiquitin-mediated disruption of the charge-dependent interaction between PB1-K578 and PB2-E72 is required to coordinate polymerase dimerization and facilitate vRNA replication, which demonstrates that IAV exploit the cellular ubiquitin system to modulate the activity of the viral polymerase for the regulation of viral replication.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:41:52.506.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD030816
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterHannes Drexler
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Influenza A virus (A/Wilson-Smith/1933(H1N1)); NCBI TaxID: 381518;
ModificationListubiquitinylated lysine; ubiquitination signature dipeptidyl lysine; iodoacetamide derivatized residue
InstrumentQ Exactive HF; LTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-07 12:42:51ID requested
12023-03-11 03:28:40announced
22023-11-14 08:41:53announced2023-11-14: Updated project metadata.
Publication List
10.6019/PXD030816;
G, ü, nl F, Krischuns T, Schreiber JA, Henschel L, Wahrenburg M, Drexler HCA, Leidel SA, Cojocaru V, Seebohm G, Mellmann A, Schwemmle M, Ludwig S, Brunotte L, The ubiquitination landscape of the influenza A virus polymerase. Nat Commun, 14(1):787(2023) [pubmed]
Keyword List
submitter keyword: Influenza A virus, PB1, affinity enrichment, PA, viral RNA-dependent RNA polymerase, ubiquitination, K-ε-GG motif,LC-MSMS, PB2
Contact List
Hannes C. A. Drexler
contact affiliationMax Planck Institute for Molecular Biomedicine Bioanalytical Mass Spectrometry Röntgenstr. 20 48149 Münster Germany
contact emailhannes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliationBioanalytical Mass Spectrometry, Max Planck Insitute for Molecular Biomedicine, Roentgenstr. 20, 48149 Münster, Germany
contact emailhannes.drexler@mpi-muenster.mpg.de
dataset submitter
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