Effects of charge on the interaction of the huntingtin N-terminal sequence with model cell membranes

Abstract

Huntington’s Disease (HD) is a genetic neurodegenerative disorder caused by an expansion in the polyglutamine (poly-Q) region near the N-terminus of the huntingtin (htt) protein. When the poly-Q expansion surpasses a threshold of 35-40 glutamine repeats, the protein misfolds into a beta sheet rich structure that forms insoluble neuronal aggregates. The poly-Q region of htt is flanked by a 17 amino acid sequence (Nt17) that facilitates insertion of htt into lipid membranes via an amphipathic alpha helical structure, a function that is proposed to anchor the protein and may affect the aggregation process.