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Updated: Apr 12, 2026

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
Published on: January 30, 2019
RNA-binding residues in the N-terminus of APOBEC3G influence its DNA sequence specificity and retrovirus restriction
Kasandra Bélanger1, Marc-André Langlois1
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Abstract:
APOBEC3G (A3G) is a host-expressed protein that inactivates retroviruses through the mutagenic deamination of cytosines (C) to uracils (U) in single-stranded DNA (ssDNA) replication products. A3G prefers to deaminate cytosines preceded by a cytosine (5'CC), whereas all other A3 proteins target cytosines in a 5'TC motifs. Structural and mutational studies have mapped the dinucleotide deamination preference of A3G to residues in loop 7 of the catalytic C-terminal domain of the protein. Here we report that A3G with a double W94A/W127A substitution in its N-terminus, designed to abolish RNA binding and protein oligomerization, alters the DNA deamination specificity of the enzyme from 5'CC to 5'TC on proviral DNA. We also show that the double substitution severely impairs its deaminase and antiretroviral activities on Vif-deficient HIV-1. Our results highlight that the N-terminal domain of the full length A3G protein has an important influence on its DNA sequence specificity and mutator activity.
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