Structural Determinants of the APOBEC3G N-Terminal Domain for HIV-1 RNA Association

APOBEC3G (A3G) is a cellular protein that inhibits HIV-1 infection through virion incorporation. The interaction of the A3G N-terminal domain (NTD) with RNA is essential for A3G incorporation in the HIV-1 virion. The interaction between A3G-NTD and RNA is not completely understood. The A3G-NTD is al...

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Published in:Frontiers in cellular and infection microbiology 2019-05, Vol.9, p.129-129
Main Authors: Fukuda, Hirofumi, Li, Songling, Sardo, Luca, Smith, Jessica L, Yamashita, Kazuo, Sarca, Anamaria D, Shirakawa, Kotaro, Standley, Daron M, Takaori-Kondo, Akifumi, Izumi, Taisuke
Format: Article
Language:English
Subjects:
APOBEC-3G Deaminase - chemistry
APOBEC-3G Deaminase - genetics
APOBEC-3G Deaminase - metabolism
APOBEC3G
Cellular and Infection Microbiology
DNA
DNA Mutational Analysis
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
HIV-1 Vif
Imaging
Molecular Docking Simulation
Protein Binding
RNA
RNA, Viral - metabolism
Structural Model
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Summary:APOBEC3G (A3G) is a cellular protein that inhibits HIV-1 infection through virion incorporation. The interaction of the A3G N-terminal domain (NTD) with RNA is essential for A3G incorporation in the HIV-1 virion. The interaction between A3G-NTD and RNA is not completely understood. The A3G-NTD is also recognized by HIV-1 Viral infectivity factor (Vif) and A3G-Vif binding leads to A3G degradation. Therefore, the A3G-Vif interaction is a target for the development of antiviral therapies that block HIV-1 replication. However, targeting the A3G-Vif interactions could disrupt the A3G-RNA interactions that are required for A3G's antiviral activity. To better understand A3G-RNA binding, we generated o docking models to simulate the RNA-binding propensity of A3G-NTD. We simulated the A3G-NTD residues with high RNA-binding propensity, experimentally validated our prediction by testing A3G-NTD mutations, and identified structural determinants of A3G-RNA binding. In addition, we found a novel amino acid residue, I26 responsible for RNA interaction. The new structural insights provided here will facilitate the design of pharmaceuticals that inhibit A3G-Vif interactions without negatively impacting A3G-RNA interactions.
ISSN:2235-2988
2235-2988
DOI:10.3389/fcimb.2019.00129