Length of polyglutamine tract affects secondary and tertiary structures of huntingtin protein

► Stability of polyglutamine stretch may determine stability of proteins. ► Normal huntingtin shows complete recovery of structure following denaturation. ► Refolding of secondary structure of denatured mutant protein is not complete. ► Tertiary structure of normal huntingtin is more stable than mutant protein. ► Aggregation of mutant huntingtin may be due to instability of polyglutamine stretch.