9IM6

Structure of influenza A virus RNA polymerase PB1 and nuclear import host factor RanBP5 complex

Summary for 9IM6

• Entry DOI: 10.2210/pdb9im6/pdb
• EMDB information: 60685
• Descriptor: Importin-5, RNA-directed RNA polymerase catalytic subunit (2 entities in total)
• Functional Keywords: virus rna polymerase, nuclear protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 132672.51

Authors

Uchikubo-Kamo, T.,Ishimoto, N.,Park, S.Y. (deposition date: 2024-07-02, release date: 2024-11-27, Last modification date: 2025-07-02)

Primary citation

Uchikubo-Kamo, T.,Ishimoto, N.,Umezawa, H.,Hirohama, M.,Ono, M.,Kawabata, H.,Kamata, K.,Ohki, M.,Yoshida, H.,Park, J.H.,Tame, J.R.H.,Kawaguchi, A.,Park, S.Y.
Structural insights into Influenza A virus RNA polymerase PB1 binding to nuclear import host factor RanBP5.
Biochem.Biophys.Res.Commun., 739:150952-150952, 2024

PubMed Abstract: 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.

PubMed: 39536408
DOI: 10.1016/j.bbrc.2024.150952

Experimental method

ELECTRON MICROSCOPY (3.21 Å)