tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2024 Nov 7:739:150952.
doi: 10.1016/j.bbrc.2024.150952. Online ahead of print. Structural insights into Influenza A virus RNA polymerase PB1 binding to nuclear import host factor RanBP5
Tomomi Uchikubo-Kamo[SUP] 1 [/SUP], Naito Ishimoto[SUP] 1 [/SUP], Haruka Umezawa[SUP] 1 [/SUP], Mikako Hirohama[SUP] 2 [/SUP], Maasa Ono[SUP] 2 [/SUP], Haruka Kawabata[SUP] 1 [/SUP], Kenichi Kamata[SUP] 1 [/SUP], Mio Ohki[SUP] 1 [/SUP], Hisashi Yoshida[SUP] 1 [/SUP], Jae-Hyun Park[SUP] 3 [/SUP], Jeremy R H Tame[SUP] 1 [/SUP], Atsushi Kawaguchi[SUP] 4 [/SUP], Sam-Yong Park[SUP] 5 [/SUP]
Affiliations
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.
. 2024 Nov 7:739:150952.
doi: 10.1016/j.bbrc.2024.150952. Online ahead of print. Structural insights into Influenza A virus RNA polymerase PB1 binding to nuclear import host factor RanBP5
Tomomi Uchikubo-Kamo[SUP] 1 [/SUP], Naito Ishimoto[SUP] 1 [/SUP], Haruka Umezawa[SUP] 1 [/SUP], Mikako Hirohama[SUP] 2 [/SUP], Maasa Ono[SUP] 2 [/SUP], Haruka Kawabata[SUP] 1 [/SUP], Kenichi Kamata[SUP] 1 [/SUP], Mio Ohki[SUP] 1 [/SUP], Hisashi Yoshida[SUP] 1 [/SUP], Jae-Hyun Park[SUP] 3 [/SUP], Jeremy R H Tame[SUP] 1 [/SUP], Atsushi Kawaguchi[SUP] 4 [/SUP], Sam-Yong Park[SUP] 5 [/SUP]
Affiliations
- PMID: 39536408
- DOI: 10.1016/j.bbrc.2024.150952
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.