7RW6

BORF2-APOBEC3Bctd Complex

Summary for 7RW6

• Entry DOI: 10.2210/pdb7rw6/pdb
• EMDB information: 24709 24715 24716
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,Ribonucleoside-diphosphate reductase large subunit, DNA dC->dU-editing enzyme APOBEC-3B, ZINC ION (3 entities in total)
• Functional Keywords: host-pathogen complex, viral protein, antiviral protein, deaminase, oxidoreductase-hydrolase complex, oxidoreductase/hydrolase
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 4
• Total formula weight: 317631.96

Authors

Shaban, N.M.,Yan, R.,Shi, K.,McLellan, J.S.,Yu, Z.,Harris, R.S. (deposition date: 2021-08-19, release date: 2022-04-27, Last modification date: 2024-10-16)

Primary citation

Shaban, N.M.,Yan, R.,Shi, K.,Moraes, S.N.,Cheng, A.Z.,Carpenter, M.A.,McLellan, J.S.,Yu, Z.,Harris, R.S.
Cryo-EM structure of the EBV ribonucleotide reductase BORF2 and mechanism of APOBEC3B inhibition.
Sci Adv, 8:eabm2827-eabm2827, 2022

PubMed Abstract: Viruses use a plethora of mechanisms to evade immune responses. A recent example is neutralization of the nuclear DNA cytosine deaminase APOBEC3B by the Epstein-Barr virus (EBV) ribonucleotide reductase subunit BORF2. Cryo-EM studies of APOBEC3B-BORF2 complexes reveal a large >1000-Å binding surface composed of multiple structural elements from each protein, which effectively blocks the APOBEC3B active site from accessing single-stranded DNA substrates. Evolutionary optimization is suggested by unique insertions in BORF2 absent from other ribonucleotide reductases and preferential binding to APOBEC3B relative to the highly related APOBEC3A and APOBEC3G enzymes. A molecular understanding of this pathogen-host interaction has potential to inform the development of drugs that block the interaction and liberate the natural antiviral activity of APOBEC3B. In addition, given a role for APOBEC3B in cancer mutagenesis, it may also be possible for information from the interaction to be used to develop DNA deaminase inhibitors.

PubMed: 35476445
DOI: 10.1126/sciadv.abm2827

Experimental method

ELECTRON MICROSCOPY (2.55 Å)