Adapted from:
Shaban, N.M., et al.
Science Advances (2022).

The background image of this website features an elegant structural solution to EBV BORF2 in complex with human APOBEC3B using cryogenic electron microscopy (cryo-EM). EBV BORF2 is the large subunit of the viral ribonucleotide reductase (RNR), which typically catalyzes the production of dNTPs, the building blocks of DNA. APOBEC3B is a cytosine deaminase, an enzyme that has the capacity to mutate viral DNA to render it defective. The structure shows a heterodimer composed of a BORF2-BORF2 dimer in the center (light and dark blue), each bound to an APOBEC3B subunit (orange) on the outside surfaces.

It reveals novel evolutionary adapations of the viral RNR to interact with and inhibit APOBEC3B. While the core domain of EBV BORF2 responsible for dNTP production is preserved, it harbors unique amino acid insertions that fold into the A3B catalytic pocket. This tight interaction inhibits A3B activity and serves as a counterdefense against A3B-induced mutagenesis. Thus, the production of EBV BORF2 during the early stages of viral replication likely serves to bolster dNTP pools as well as protect newly synthesized DNA against the host defense protein APOBEC3B.

For additional information, please review the original article as well as prior mechanistic studies.

Generated by Adam Z. Cheng using RCSB PDB Mol* 3D Viewer using PDB 7RW6.
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