Dr. Jerry LaRue
The World Health Organization found that 37.9 million people were living with HIV by the end of 2018. HIV is a virus that weakens the immune system through viral replication and the destruction of CD4+ T-cells, which are white blood cells that detect infection and make antibodies. A cure for HIV has not yet been discovered. HIV-1 contains a Gag polyprotein which regulates the stages of viral replication. Previous studies suggest that the myristoyl group of a matrix protein peptide found on the Gag polyprotein, MA, forms a complex with a calcium-binding, multifunctional regulatory protein called Calmodulin (CaM). CaM has also been found to be upregulated upon HIV infection. The MA/CaM complex induces extended conformation and causes a decrease in the compact structure of MA, which is predicted to impact the accessibility of interaction sites within MA and lead to rapid HIV viral production. Through hindering the myristoyl group on MA, it is possible that production of HIV can be greatly decreased. Before exploring this possibility, it is first necessary that the site and mechanism of the protein-protein interaction is identified and understood. For this reason, our lab is investigating the interactions of the independent N-terminal and C-terminal domains of MA and CaM. The MA protein has tryptophan-containing helices on its domains which allows for quantification using fluorescence spectroscopy and anisotropy. By investigating each protein domain and tryptophan signal separately, the location where binding occurs can be isolated and it can be determined if the interaction of one CaM or MA domain is required, or a prerequisite, for the interaction of the other. Identifying how each protein domain is involved enhances current understanding of HIV production and is a significant step in determining a possible solution for inhibiting HIV-1 replication.
Kendall, Riley K. and LaRue, Jerry, "Investigating the Interactions Between Individual Calmodulin and HIV-1 Protein Domains" (2020). Student Scholar Symposium Abstracts and Posters. 383.
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