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.
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