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タイトル: | Structural Determinants of the APOBEC3G N-Terminal Domain for HIV-1 RNA Association |
著者: | Fukuda, Hirofumi Li, Songling Sardo, Luca Smith, Jessica L. Yamashita, Kazuo Sarca, Anamaria D. Shirakawa, Kotaro https://orcid.org/0000-0002-7469-1276 (unconfirmed) Standley, Daron M. Takaori-Kondo, Akifumi Izumi, Taisuke |
著者名の別形: | 福田 寛文 白川, 康太郎 髙折, 晃史 |
キーワード: | APOBEC3G RNA DNA HIV-1 Vif Structural Model Imaging |
発行日: | 21-May-2019 |
出版者: | Frontiers Media SA |
誌名: | Frontiers in cellular and infection microbiology |
巻: | 9 |
論文番号: | 129 |
抄録: | 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 in silico 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. |
著作権等: | © 2019 Fukuda, Li, Sardo, Smith, Yamashita, Sarca, Shirakawa, Standley, Takaori-Kondo and Izumi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
URI: | http://hdl.handle.net/2433/243757 |
DOI(出版社版): | 10.3389/fcimb.2019.00129 |
PubMed ID: | 31165049 |
出現コレクション: | 学術雑誌掲載論文等 |
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