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TitleStructural insights into Influenza A virus RNA polymerase PB1 binding to nuclear import host factor RanBP5.
Journal, issue, pagesBiochem Biophys Res Commun, Vol. 739, Page 150952, Year 2024
Publish dateNov 7, 2024
AuthorsTomomi Uchikubo-Kamo / Naito Ishimoto / Haruka Umezawa / Mikako Hirohama / Maasa Ono / Haruka Kawabata / Kenichi Kamata / Mio Ohki / Hisashi Yoshida / Jae-Hyun Park / Jeremy R H Tame / Atsushi Kawaguchi / Sam-Yong Park /
PubMed AbstractThe genome of influenza A viruses consists of eight RNA segments that form a heterotrimer, and the viral genome undergoes transcription and replication in the nucleus. Thus, during infection, newly ...The genome of influenza A viruses consists of eight RNA segments that form a heterotrimer, and the viral genome undergoes transcription and replication in the nucleus. Thus, during infection, newly synthesized RNA polymerase subunits must be imported into the nucleus. Although several models have been proposed for this process, the consensus is that the RNA polymerase subunits PB1 and PA form a dimer in the cytoplasm and are transported into the nucleus by Ran binding protein 5 (RanBP5). The PB2 subunit undergoes separate transport to complete the nuclear import. However, the molecular mechanism of nuclear import by host factors and their interactions with proteins are largely unknown. Here we present the structural analysis of the RanBP5 and PB1 NLS domain complex by cryo-EM at 3.2 Å resolution. The pattern shows that the NLS domain of PB1 does not exist in a secondary structure and interacts with RanBP5 in a wrapped state. In addition, biochemical analyses of the mutant have identified critical amino acid sites involved in complex binding. The results suggest a stepwise assembly of influenza virus structural components regulated by nuclear import mechanisms and host factor binding, with important implications for drug discovery research.
External linksBiochem Biophys Res Commun / PubMed:39536408
MethodsEM (single particle)
Resolution3.21 Å
Structure data

60685

9im6

EMDB-60685, PDB-9im6:
Structure of influenza A virus RNA polymerase PB1 and nuclear import host factor RanBP5 complex
Method: EM (single particle) / Resolution: 3.21 Å

Source
  • homo sapiens (human)
  • influenza a virus (strain a/puerto rico/8/1934 h1n1)
  • Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
KeywordsNUCLEAR PROTEIN / virus RNA polymerase

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