APOBEC3G DNA deaminase acts processively 3' --> 5' on single-stranded DNA.
Akin to a 'Trojan horse,' APOBEC3G DNA deaminase is encapsulated by the HIV virion. APOBEC3G facilitates restriction of HIV-1 infection in T cells by deaminating cytosines in nascent minus-strand complementary DNA. Here, we investigate the biochemical basis for C --> U targeting. We observe that APOBEC3G binds randomly to single-stranded DNA, then jumps and slides processively to deaminate target motifs. When confronting partially double-stranded DNA, to which APOBEC3G cannot bind, sliding is lost but jumping is retained. APOBEC3G shows catalytic orientational specificity such that deamination occurs predominantly 3' --> 5' without requiring hydrolysis of a nucleotide cofactor. Our data suggest that the G --> A mutational gradient generated in viral genomic DNA in vivo could result from an intrinsic processive directional attack by APOBEC3G on single-stranded cDNA.
Chelico
Linda
L
Department of Biological Sciences Molecular and Computational Section, University of Southern California, Los Angeles, California 90089-2910, USA.
Pham
Phuong
P
Calabrese
Peter
P
Goodman
Myron F
MF
D000071480:APOBEC-3G Deaminase; D000586:Amination; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002460:Cell Line; D003564:Cytidine Deaminase; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera; D013379:Substrate Specificity
D004277:DNA, Single-Stranded; D012097:Repressor Proteins; D012313:RNA; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase