Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a mutation in the huntingtin (htt) gene. At one end of the htt gene, a tract of DNA sequence containing a region of sequence repeat is expanded. This means that the corresponding protein made from the gene has an expanded region at one end of the huntingtin protein. The repeated amino acid of the protein sequence is glutamine (Q) so this is referred to as a polyQ expansion. 

Affecting approximately 1 in 100,000 individuals, the symptom onset is earlier and the symptom severity greater with larger gene expansion mutations. HD patients suffer from a range of symptoms broadly characterised by motor dysfunctions, cognitive disability and psychiatric disturbance. There are currently no therapies available to either cure this disease or effectively treat symptoms.

Our understanding of the HTT protein is still fairly basic. We know that it plays an important role in neural cell development and is involved in transport within the cell. We also know that it is likely a scaffold for other important proteins to bind on to. As a structural biologist, I am interested in what protein molecule look like i.e. how are all of the atoms in the protein connected and arranged in 3D space. By understanding what protein molecules look like we can often infer what their functions are and how these might change in the context of a mutation, in the case of HD, a polyQ expansion. As such, structural studies of HTT protein would be useful in providing a greater understanding of HD biochemistry.