APOBEC3 proteins: Potential host-encoded antiviral targets
Residues conserved among APOBEC3G and 3A are shown in silver.
Cytidine deaminases edit nucleic acids by deaminating cytidines to uridines and are evolutionarily conserved. The biochemical simplicity of cytidine deamination mechanism has enabled AID/APOBEC proteins to evolve into powerful polynucleotide mutators. AID and the APOBEC3 proteins play key roles as DNA mutators in humoral immunity during antigen-driven antibody diversification as well as in innate antiviral and antibacterial defense. APOBEC3G/F/H exert antiretroviral effect by being incorporated into viral particles and introducing point mutations into the viral genome, thus disabling the production of functional viral proteins upon subsequent infection.
APOBEC3A, an extremely potent DNA mutator, degrades foreign DNA in phagocytic cells and have recently been shown to play a role cancer development. Furthermore, AID/APOBEC3 proteins may play a crucial role in DNA demethylation. The essential mechanistic aspects underlying this diverse set of actions are not well understood, primarily due to the lack of reliable structural information on almost all AID/APOBEC family members. None of the quintessential interactions that define specificity to binding partners or susceptibility to antagonistic proteins are well delineated. APOBEC2 and the C-terminal domain of human APOBEC3G are the only members of this class for which high-resolution structures are available. Our work is focused on understanding the structural basis of mechanisms underlying antiviral activity of APOBEC3 proteins and subsequent application of structural information to novel antiviral approaches.