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| Title | Structural insights into the dynamic mechanism of bornavirus polymerase. |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 122, Issue 39, Page e2504779122, Year 2025 |
| Publish date | Sep 30, 2025 |
Authors | Ge Yang / Dong Wang / Bin Liu / ![]() |
| PubMed Abstract | Borna disease virus 1 (BoDV-1), an emerging zoonotic pathogen from the family, is neurotropic and can infect a variety of mammalian hosts, including humans. Linked to severe encephalitis and high ...Borna disease virus 1 (BoDV-1), an emerging zoonotic pathogen from the family, is neurotropic and can infect a variety of mammalian hosts, including humans. Linked to severe encephalitis and high mortality, BoDV-1 currently lacks licensed treatments or vaccines. The BoDV-1 polymerase complex, comprising the large (L) and phosphoprotein (P) subunits, is crucial for viral replication and transcription, making it a promising target for antiviral intervention. Here, we present the cryoelectron microscopy structure of the apo BoDV-1 L-P complex, revealing a unique "mitten-shaped" architecture. The structure characterizes key domains involved in RNA synthesis, including RNA-dependent RNA polymerase, polyribonucleotidyltransferase, and an inactive methyltransferase domain. While no RNA or NTPs were visible, we observed distinct conformational states, showing large-scale rearrangements of the P tetramer and L domains, as well as remodeling of the RNA template, nucleoside triphosphates, and nascent RNA entrances and/or exits, upon introducing RNA and NTPs. These findings highlight the dynamic structural changes probably associated with polymerase activity and advance the understanding of the BoDV-1 polymerase mechanisms, offering a basis for developing targeted antiviral strategies against this deadly pathogen. |
External links | Proc Natl Acad Sci U S A / PubMed:40996804 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.71 - 3.47 Å |
| Structure data | EMDB-48790, PDB-9n0q: EMDB-48791, PDB-9n0r: EMDB-48792, PDB-9n0s: EMDB-48793, PDB-9n0t: EMDB-48794, PDB-9n0u: |
| Chemicals | ![]() ChemComp-ZN: |
| Source |
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Keywords | TRANSFERASE / VIRAL PROTEIN / Bornavirus / L protein / phosphoprotein / RNA-dependent RNA polymerase / PRNTase / GDP polyribonucleotidyl transferase / RNA capping / viral replication |
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