We have identified a domain in the N terminus of huntingtin that binds to membranes. A
three-dimensional homology model of the structure of the binding domain predicts helical
HEAT repeats, which emanate a positive electrostatic potential, consistent with a charge-
based mechanism for membrane association. An amphipathic helix capable of inserting into
pure lipid bilayers may serve to anchor huntingtin to the membrane. In cells, N-terminal
huntingtin fragments targeted to regions of plasma membrane enriched in …