Currently, I am continuing to work on the domain mapping experiments with huntingtin (HTT) protein. I hope that by working out more about the domain organisation of this protein, I will be able to infer information about its 3-dimensional structure (what does it look like?) and maybe its functions in the cell (what is it doing in neurons?) to guide a greater understanding of the biochemistry of Huntington’s disease. You can now look through the data and some brief analysis. Please feel free to comment or email me if you have any questions about this work.
I have also been reading more about HTT proteolysis in disease models and how this contributes to the HD phenotype. N-terminal fragments produced by HTT cleavage have been linked previously to nuclear toxicity in many studies. A more recent study by El-Daher et al in EMBO provides evidence supporting a role for the resultant C-terminal fragments in cellular toxicity and that specific HTT cleavage events disrupt protein-protein interactions. The evidence points to a normal role of huntingtin in ER homeostasis and dynamin-1 function. I am now researching more into HTT cleavage sites identified by different groups in different model systems to see how this correlates with domain boundaries I identify with my biochemical analysis.