The objective of this research is to investigate the role of HIV-1 and other retroviral Gag and nucleocapsid proteins (NC) in the regulation of processes involving nucleic acid structural transitions and viral self assembly in retroviral systems. Single molecule DNA stretching experiments can induce the DNA helix-coil transition. Investigation of the effects of retroviral NC proteins on this transition has shed light on the mechanism of nucleic acid chaperone activity. We will investigate these interactions by examining the effects of NC from HIV-1 and other retroviruses as well as HIV-1 Gag proteins on DNA packaging and the DNA helix-coil transition. We will use this novel technique to probe the effects of drugs on the capability of NC proteins to alter DNA melting, it has also been shown that specific structures of DNA and RNA can be probed using force spectroscopy. We will extend this technique to study the interactions of retroviral NC and Gag proteins with specific RNA structures that are important for retroviral replication. We will then develop a quantitative model for the interaction of retroviral NC and Gag proteins with nucleic acids, which will increase our understanding of nucleic acid chaperone activity and viral assembly. The 3 specific aims are: 1. To probe the nucleic acid chaperone activity of retroviral nucleocapsid proteins and the viral self-assembly of Gag proteins. 2. To probe the capabilities of NC binding drugs to alter NC's nucleic acid chaperone activity. 3. To probe the interaction of retroviral nucleocapsid and Gag proteins with HIV-1 RNA structures.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
AIDS Molecular and Cellular Biology Study Section (AMCB)
Program Officer
Lewis, Catherine D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northeastern University
Schools of Arts and Sciences
United States
Zip Code
Naufer, M Nabuan; Furano, Anthony V; Williams, Mark C (2018) Protein-nucleic acid interactions of LINE-1 ORF1p. Semin Cell Dev Biol :
McCauley, Micah J; Rouzina, Ioulia; Williams, Mark C (2018) Constructing Free Energy Landscapes of Nucleic Acid Hairpin Unfolding. Methods Mol Biol 1811:315-332
Feng, Yuqing; Wong, Lai; Morse, Michael et al. (2018) RNA-Mediated Dimerization of the Human Deoxycytidine Deaminase APOBEC3H Influences Enzyme Activity and Interaction with Nucleic Acids. J Mol Biol 430:4891-4907
Morse, Michael; Huo, Ran; Feng, Yuqing et al. (2017) Dimerization regulates both deaminase-dependent and deaminase-independent HIV-1 restriction by APOBEC3G. Nat Commun 8:597
Murugesapillai, Divakaran; Bouaziz, Serge; Maher, L James et al. (2017) Accurate nanoscale flexibility measurement of DNA and DNA-protein complexes by atomic force microscopy in liquid. Nanoscale 9:11327-11337
Almaqwashi, Ali A; Paramanathan, Thayaparan; Rouzina, Ioulia et al. (2016) Mechanisms of small molecule-DNA interactions probed by single-molecule force spectroscopy. Nucleic Acids Res 44:3971-88
Almaqwashi, Ali A; Andersson, Johanna; Lincoln, Per et al. (2016) Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation. Biophys J 110:1255-63
Post, Klara; Olson, Erik D; Naufer, M Nabuan et al. (2016) Mechanistic differences between HIV-1 and SIV nucleocapsid proteins and cross-species HIV-1 genomic RNA recognition. Retrovirology 13:89
Naufer, M Nabuan; Callahan, Kathryn E; Cook, Pamela R et al. (2016) L1 retrotransposition requires rapid ORF1p oligomerization, a novel coiled coil-dependent property conserved despite extensive remodeling. Nucleic Acids Res 44:281-93
Almaqwashi, Ali A; Andersson, Johanna; Lincoln, Per et al. (2016) DNA intercalation optimized by two-step molecular lock mechanism. Sci Rep 6:37993

Showing the most recent 10 out of 52 publications