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A3B also contributes to mutagenesis and genome instability in cancer cells, driving tumor evolution and detrimental outcomes including therapy resistance and metastasis. A3B comprises tandem globular deaminase domains, with a multifunctional amino-terminal domain (NTD) and a catalytically active carboxy-terminal domain (CTD). Although individual domain structures have been studied, the structure of full-length A3B has remained elusive. Here, we report the cryoEM structure of wildtype A3B in complex with the natural antagonist BORF2 (the large subunit of the Epstein-Barr virus ribonucleotide reductase). The two domains of A3B bridge a novel BORF2 dimer interface, showing a unique domain positioning that distinguishes A3B from the related dual-domain retrovirus restriction factor APOBEC3G (A3G). Mutational analyses suggest that the unique NTD-CTD interaction regulates A3B deaminase activity. The BORF2 dimerization interface is stabilized by primary interactions with A3B-CTD and secondary contacts with A3B-NTD, as well as by A3B CTD-CTD dimerization. This matrix of interactions supports a molecular mechanism for A3B neutralization in which BORF2 binding leads to deaminase sequestration in large aggregates. The full-length wildtype A3B structure also provides a platform for future anti-viral and anti-cancer drug development efforts.<\/jats:p>","DOI":"10.64898\/2026.06.18.733170","type":"posted-content","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:40:26Z","timestamp":1781872826000},"source":"Crossref","is-referenced-by-count":0,"title":["Full-length structure of the anti-viral and pro-tumor DNA deaminase APOBEC3B"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-3244","authenticated-orcid":false,"given":"Ryan H.","family":"Abdella","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA, 55455"},{"name":"Characterization Facility, University of Minnesota, Minneapolis, MN, USA, 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8492-4427","authenticated-orcid":false,"given":"Christopher 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