8pm0
From Proteopedia
Influenza A/H7N9 polymerase in replicase-like conformation in pre-initiation state with Pol II pS5 CTD peptide mimic bound in site 1A/2A
Structural highlights
FunctionX5F427_9INFA Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex.[HAMAP-Rule:MF_04062][SAAS:SAAS01109044] Publication Abstract from PubMedThe current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription or replication of the viral genome, respectively. Here, we provide evidence that the FluPol-RNAP II binding interface, beyond its well-acknowledged function in cap-snatching during transcription initiation, has also a pivotal role in replication of the viral genome. Using a combination of cell-based and in vitro approaches, we show that the RNAP II C-terminal-domain, jointly with ANP32, enhances FluPol replication activity. We observe successive conformational changes to switch from a transcriptase to a replicase conformation in the presence of the bound RNPAII C-terminal domain and propose a model in which the host RNAP II is the anchor for transcription and replication of the viral genome. Our data open new perspectives on the spatial coupling of viral transcription and replication and the coordinated balance between these two activities. The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome.,Krischuns T, Arragain B, Isel C, Paisant S, Budt M, Wolff T, Cusack S, Naffakh N Nat Commun. 2024 Feb 5;15(1):1064. doi: 10.1038/s41467-024-45205-2. PMID:38316757[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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