Date of Award

Winter 1993

Project Type

Dissertation

Program or Major

Biochemistry

Degree Name

Doctor of Philosophy

First Advisor

Thomas M Laue

Abstract

Retroviral Integration Protein (IN) has been shown to be both necessary and sufficient for the integration of reverse transcribed retroviral DNA into the host cell DNA. It has been demonstrated that self-association is required for proper function, yet little is known about the thermodynamic properties of this association. Analytical ultracentrifugation was used to determine the stoichiometries and free energies ($\Delta$G) of IN self association under various physical conditions. The best fit model of association in all glycerol-free conditions studied was a reversible monomer-dimer-tetramer. The addition of glycerol at concentrations of 8% (vol/vol) or greater significantly enhances the monomer-dimer formation so that the best fit model is dimer-tetramer.

The data support a model in which distinct binding sites on the protein are responsible for monomer-dimer and dimer-tetramer association. The strength of the association is influenced by hydrogen bonding as well as charge-charge, dipole and hydrophobic interactions. The understanding of the thermodynamics of IN association may aid in targeting this protein for therapeutic intervention.

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