Nanoscale Characterization of Interaction of APOBEC3G with RNA

Yangang Pan, Zhiqiang Sun, Atanu Maiti, Tapan Kanai, Hiroshi Matsuo, Ming Li, Reuben S. Harris, Luda S. Shlyakhtenko, Yuri L Lyubchenko

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The human cytidine deaminase APOBEC3G (A3G) is a potent inhibitor of the HIV-1 virus in the absence of viral infectivity factor (Vif). The molecular mechanism of A3G antiviral activity is primarily attributed to deamination of single-stranded DNA (ssDNA); however, the nondeamination mechanism also contributes to HIV-1 restriction. The interaction of A3G with ssDNA and RNA is required for its antiviral activity. Here we used atomic force microscopy to directly visualize A3G-RNA and A3G-ssDNA complexes and compare them to each other. Our results showed that A3G in A3G-RNA complexes exists primarily in monomeric-dimeric states, similar to its stoichiometry in complexes with ssDNA. New A3G-RNA complexes in which A3G binds to two RNA molecules were identified. These data suggest the existence of two separate RNA binding sites on A3G. Such complexes were not observed with ssDNA substrates. Time-lapse high-speed atomic force microscopy was applied to characterize the dynamics of the complexes. The data revealed that the two RNA binding sites have different affinities for A3G. On the basis of the obtained results, a model for the interaction of A3G with RNA is proposed.

Original languageEnglish (US)
Pages (from-to)1473-1481
Number of pages9
JournalBiochemistry
Volume56
Issue number10
DOIs
Publication statusPublished - Mar 14 2017

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