Original Research ARTICLE
Structural Determinants of the APOBEC3G N-terminal domain for HIV-1 RNA association
- 1Department of Hematology and Oncology, Kyoto University, Japan
- 2Systems Immunology Laboratory, WPI Research Center Immunology Frontier Research Center and Department of Genome Informatics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Japan
- 3Systems Immunology Laboratory, WPI Research Center Immunology Frontier Research Center, Osaka University, Japan
- 4Department of Biological Sciences, McNeil Science and Technology Center, University of the Sciences, United States
- 5Molecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), United States
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 represents a novel target for the development of antiviral therapies that block HIV 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 the A3G-RNA binding. The new structural insights provided here will facilitate the design of pharmaceuticals that inhibit A3G-Vif interactions without negatively impacting A3G-RNA interactions.
Keywords: APOBEC3G (A3G), HIV-1 Vif, RNA, Structural model, imaging
Received: 17 Feb 2019;
Accepted: 11 Apr 2019.
Edited by:Jean-Christophe Paillart, Université de Strasbourg, France
Reviewed by:Santiago Guerrero, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Ecuador
Alessia Zamborlini, Conservatoire National des Arts et Métiers (CNAM), France
Linda Chelico, University of Saskatchewan, Canada
Copyright: © 2019 Fukuda, Songling, Yamashita, Sardo, Smith, 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.
* Correspondence: PhD. Taisuke Izumi, Kyoto University, Department of Hematology and Oncology, Kyoto, 606-8501, Kyōto, Japan, firstname.lastname@example.org