Crystal structure of the C-terminal deaminase domain of APOBEC3G: Implications and projections

APOBEC3 proteins belong to a family of cytidine deaminases that can inhibit a variety of retroviruses as well as a range of endogenous retroelements. In particular, APOBEC3G can strongly restrict HIV-1 Vif deletion mutants. Normally, however, HIV-1 counters this restriction by using the viral protein Vif to direct the degradation of APOBEC3 proteins by targeting them for proteasomal degradation. However, in the absence of Vif, APOBEC3G can be packaged into virions and, upon re-infection of new cells, can induce C-to-U mutations in the newly reverse-transcribed, ssDNA. Understanding the structural elements of APOBEC3 proteins, their mechanism of action and how they interact with proteins such as HIV-1 Vif, is crucial for intelligent drug design. In this recently published manuscript, the crystal structure of the C-terminal deaminase domain of APOBEC3GC-terminal deaminase domain (CDD) is reported. They compare their crystal structure with that of APOBEC2, another member of the APOEBC family, as well as a previously published nuclear magnetic resonance structure of APOBEC3G-CDD. Additional structural features that may be involved in the enzyme's mechanism of action, processivity and directionality are described.