RNA-Dependent Oligomerization of APOBEC3G Is Required for Restriction of HIV-1

• DOI: 10.1371/journal.ppat.1000330
• Publication Date: 2009-03-06T02:02:40Z
• Authors: Hendrik Huthoff; Flavia Autore; Sarah Gallois-Mon...; Franca Fraternali; Michael H. Malim
• Keywords: APOBEC3G; Cytidine; Activation-induced (cytidine) deaminase; Deamination

The human cytidine deaminase APOBEC3G (A3G) is a potent inhibitor of retroviruses and transposable elements able to deaminate cytidines uridines in single-stranded DNA replication intermediates. A3G contains two canonical domains (CDAs), which only the C-terminal one known mediate deamination. By exploiting crystal structure related tetrameric APOBEC2 (A2) protein, we identified residues within that have potential oligomerization protein. Using yeast two-hybrid assays, co-immunoprecipitation, chemical crosslinking, show tyrosine-124 tryptophan-127 enzymatically inactive N-terminal CDA domain oligomerization, this coincides with packaging into HIV-1 virions. In addition importance specific A3G, also shown be RNA-dependent. Homology modelling onto A2 template indicates an accumulation positive charge pocket formed by putative dimer interface. Substitution arginine at positions 24, 30, 136 resulted reduced virus inhibition, virion packaging, oligomerization. Consistent RNA serving central role all these activities, oligomerization-deficient proteins associated less efficiently several cellular molecules. Accordingly, propose occupation positively charged promotes virions antiviral function.