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-Structure paper
Title | Cryo-EM structure of the EBV ribonucleotide reductase BORF2 and mechanism of APOBEC3B inhibition. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 17, Page eabm2827, Year 2022 |
Publish date | Apr 29, 2022 |
Authors | Nadine M Shaban / Rui Yan / Ke Shi / Sofia N Moraes / Adam Z Cheng / Michael A Carpenter / Jason S McLellan / Zhiheng Yu / Reuben S Harris / |
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 ...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. |
External links | Sci Adv / PubMed:35476445 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.55 - 2.82 Å |
Structure data | EMDB-24709: Composite Map BORF2-APOBEC3Bctd Complex EMDB-24715: Focused Refined Map BORF2-APOBEC3Bctd Complex EMDB-24716: BORF2-APOBEC3Bctd Complex |
Chemicals | ChemComp-ZN: |
Source |
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Keywords | OXIDOREDUCTASE/HYDROLASE / Host-pathogen complex / viral protein / antiviral protein / deaminase / OXIDOREDUCTASE-HYDROLASE complex |