9N0R

2.71A Bornavirus L-P complex (after incubation with RNA/NTP) (state 1)

Summary for 9N0R

• Entry DOI: 10.2210/pdb9n0r/pdb
• EMDB information: 48791
• Descriptor: RNA-directed RNA polymerase, P protein, ZINC ION (3 entities in total)
• Functional Keywords: bornavirus, l protein, phosphoprotein, rna-dependent rna polymerase, prntase, gdp polyribonucleotidyl transferase, rna capping, viral replication, transferase, viral protein
• Biological source: Orthobornavirus; More
• Total number of polymer chains: 5
• Total formula weight: 281857.83

Authors

Liu, B.,Yang, G.,Wang, D. (deposition date: 2025-01-24, release date: 2025-09-10, Last modification date: 2025-10-15)

Primary citation

Yang, G.,Wang, D.,Liu, B.
Structural insights into the dynamic mechanism of bornavirus polymerase.
Proc.Natl.Acad.Sci.USA, 122:e2504779122-e2504779122, 2025

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 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.

PubMed: 40996804
DOI: 10.1073/pnas.2504779122

Experimental method

ELECTRON MICROSCOPY (2.71 Å)