UBC Theses and Dissertations
Investigating the protein-protein interactions between TAR DNA-binding protein 43 AND p65 subunit of NF-κB Lee, Joseph
TAR DNA-binding Protein 43 (TDP-43), a ubiquitous protein that regulates gene expression, has been found to play a crucial role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), in which the disease is characterized by TDP-43 protein inclusion bodies. Relevant literature suggests that the protein either self-aggregates or interacts with various partners to cause this proteinopathy. One of these binding partners was suggested to be the p65 domain of the nuclear factor kappa-B (NF-κB), a transcription protein complex which plays a crucial role in inflammatory and immune responses. It is upon this hypothetical disease pathogenesis that the study of TDP-43 and NF-κB p65 is rationalized. Hence, the first part of the thesis describes the methods that were developed to obtain pure recombinant TDP-43 from an E.coli expression system. Subsequently, the preparation of NF-κB p65 peptides using solid phase peptide synthesis (SPSS) is described in the thesis. Furthermore, the structural conformation of proteins and peptides was explored using molecular dynamics (MD) simulations to predict how they will behave in vivo and also to allow a comparison to in vitro experimentation.
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