Nature Structural & Molecular Biology 13, 392 - 399 (2006)
Published online: 23 April 2006; | doi:10.1038/nsmb1086
APOBEC3G DNA deaminase acts processively 3'  5' on single-stranded DNALinda Chelico, Phuong Pham, Peter Calabrese
& Myron F Goodman
Department of Biological Sciences Molecular and Computational Section, University of Southern California, Los Angeles, California 90089-2910, USA.
Correspondence should be addressed to Myron F Goodman mgoodman@usc.edu 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.
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