9X28

Cryo-EM structure of Borna disease virus RNA polymerase L protein

Summary for 9X28

• Entry DOI: 10.2210/pdb9x28/pdb
• Related: 9X1V
• EMDB information: 66473
• Descriptor: RNA-directed RNA polymerase L (1 entity in total)
• Functional Keywords: polymerase, viral protein
• Biological source: Borna disease virus-V
• Total number of polymer chains: 1
• Total formula weight: 194970.88

Authors

Ma, J.,Yang, K.,Wu, H.,Liang, Z. (deposition date: 2025-10-04, release date: 2026-06-10)

Primary citation

Yang, K.,Wu, H.,Liang, Z.,Zou, J.,Ma, J.
Structural mechanism of Borna disease virus 1 RNA polymerase autoinhibition and suramin-mediated inhibition.
Cell Rep, 45:117462-117462, 2026

PubMed Abstract: Borna disease virus 1 (BoDV-1) is a neurotropic pathogen that causes severe, often fatal encephalitis, yet effective treatments remain unavailable. As a nuclear-replicating mononegavirus, BoDV-1 employs a minimal L-P polymerase complex. Here, we report cryo-electron microscopy (cryo-EM) structures of the BoDV-1 polymerase in L-alone, apo-L-P, and inhibitor-bound L-P states, revealing the most compact L protein characterized among mononegaviruses. While the catalytic core is conserved, the C-terminal domains are degenerate, with the methyltransferase-like (MTase-like) domain lacking canonical functional motifs. We identify an N-terminal autoinhibitory element (AIE) that is positioned to physically block the template entry tunnel, suggesting an autoinhibition mechanism reminiscent of a "molecular plug." Furthermore, we demonstrate that the inhibitor suramin binds in a specific triple-molecule mode, potentially achieving inhibition by sterically occluding RNA access and allosterically restricting the catalytic core. These findings elucidate the architecture and regulation of the BoDV-1 polymerase, providing a structural framework for rational antiviral design.

PubMed: 42213784
DOI: 10.1016/j.celrep.2026.117462

Experimental method

ELECTRON MICROSCOPY (2.83 Å)